43 results on '"AVERNA MR"'
Search Results
2. CLINICAL AND MOLECULAR CHARACTERIZATION OF HYPERCHOLESTEROLEMIC SICILIAN FAMILIES AND DESCRIPTION OF 3 NOVEL MUTATIONS IN THE LDLR GENE
- Author
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VIVONA, Nicoletta, MINA', Mariangela, VALENTI, Vincenza, POLLACCIA, Daniela, SPINA, Rossella, BARBAGALLO, Carlo Maria, CEFALU', Angelo Baldassare, NOTARBARTOLO, Alberto, AVERNA, Maurizio, DITTA, M, NOTO, D, VIVONA, N, DITTA, M, MINA, M, VALENTI, V, POLLACCIA, D, SPINA, R, BARBAGALLO, CM, NOTO, D, CEFALU, AB, NOTARBARTOLO, A, and AVERNA, MR
- Published
- 2007
3. SHORT APOB TRUNCATIONS SHOW IMPAIRE CHYLOMICRON EXPORT AND ENTEROCYTE TRIGLYCERIDE ACCUMULATION. IN VIVO AND IN VITRO EVIDENCE ON A APOB 28.25 STABLE-TRANSFECTED ENTEROCYTE CELL LINE
- Author
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CANNIZZARO, Alessandra, FAYER, Francesca, NOTO D, CEFALU', Angelo Baldassare, MONTALCINI T, VALENTI, Vincenza, PITRONE M, MINA', Mariangela, BARRACO, Giacoma, NOTARBARTOLO, Alberto, PUJIA A, AVERNA, Maurizio, CANNIZZARO A, FAYER F, NOTO D, CEFALU AB, MONTALCINI T, VALENTI V, PITRONE M, MINA M, BARRACO G, NOTARBARTOLO A, PUJIA A, and AVERNA MR
- Subjects
FHBL ,CHYLOMICRON ,APOB - Published
- 2007
4. HYPERTENSION AND DIABETES MELLITUS PREDICT CARDIOVASCULAR EVENTS IN ELDERLY WITHOUT CARDIOVASCULARDISEASE. RESULTS OF FIFTEEN YEARS FOLLOW-UP IN A MEDITERRANEAN POPULATION
- Author
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FALLETTA A, NOTO D, SAPIENZA M, CAVERA G, PAGANO M, ALAIMO V, RINELLAMR, CEFALU', Angelo Baldassare, BARBAGALLO, Carlo Maria, NOTARBARTOLO, Alberto, AVERNA, Maurizio, FALLETTA A, NOTO D, CEFALU AB, BARBAGALLO CM, SAPIENZA M, CAVERA G, PAGANO M, ALAIMO V, RINELLAMR, NOTARBARTOLO A, and AVERNA MR
- Published
- 2007
5. ΒETA ARRESTIN-2: A NEW 'ACTOR' IN THE LDL-R ENDOCYTOSIS?
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VIVONA, Nicoletta, FAYER, Francesca, MINA', Mariangela, VALENTI, Vincenza, POLLACCIA, Daniela, SPINA, Rossella, CEFALU', Angelo Baldassare, NOTARBARTOLO, Alberto, AVERNA, Maurizio, DITTA, M, NOTO, D, VIVONA, N, DITTA, M, FAYER, F, MINA, M, VALENTI, V, POLLACCIA, D, SPINA, R, NOTO, D, CEFALU, AB, NOTARBARTOLO, A, and AVERNA, MR
- Published
- 2007
6. GENETIC HETEROGENEITY OF SEVERE HYPOBETALIPOPROTEINEMIA
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DI LEO E, MAGNOLO L, PINOTTI E, NOTO D, TARUGI P., CEFALU', Angelo Baldassare, AVERNA, Maurizio, DI LEO E, MAGNOLO L, PINOTTI E, CEFALU AB, NOTO D, AVERNA MR, and TARUGI P
- Published
- 2007
7. INTERLEUKIN 6 PLASMA LEVELS PREDICT WITH HIGH SENSITIVITY AND SPECIFICITY CORONARY STENOSIS DETECTED BY CORONARY ANGIOGRAPHY
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MAGGIORE, Maria, CEFALU', Angelo Baldassare, VADALA', Anna, BARBAGALLO, Carlo Maria, PERNICE, Valentina, MINA', Mariangela, FAYER, Francesca, CERASOLA, Giovanni, NOTARBARTOLO, Alberto, AVERNA, Maurizio, NOTO D, COTTONE S, RIZZO M, MAGGIORE M, NOTO D, COTTONE S, CEFALU AB, VADALA A, BARBAGALLO CM, RIZZO M, PERNICE V, MINA M, FAYER F, CERASOLA G, NOTARBARTOLO A, and AVERNA MR
- Published
- 2007
8. CARDIOVASCULAR RISK FACTORS ANALYSIS OF PEDIATRIC MATABOLIC SYNDROME
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CEFALU', Angelo Baldassare, FERTITTA, Emanuela, CARDELLA, Graziella, NOTARBARTOLO, Alberto, AVERNA, Maurizio, MARTINO, Fabrizio, NIGLIO T, NOTO D, MARTINO E, DI BELLA F, CEFALU AB, NIGLIO T, NOTO D, MARTINO E, DI BELLA F, FERTITTA E, CARDELLA G, NOTARBARTOLO A, AVERNA MR, and MARTINO F
- Published
- 2007
9. INTERACTION OF THE INTRACELLULAR DOMAIN OF THE LOW DENSITY LIPOPROTEIN (LDL) RECPTOR WITH METALLOTHIONEIN2 (MT2)
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POLLACCIA, Daniela, COSTA, Salvatore, NICOSIA, Aldo, VALENTI, Vincenza, SPINA, Rossella, VIVONA, Nicoletta, CEFALU', Angelo Baldassare, NOTARBARTOLO, Alberto, AVERNA, Maurizio, RAGUSA, Maria Antonietta, DITTA, M, GIANGUZZA, Fabrizio, NOTO, D, POLLACCIA, D, COSTA, S, NICOSIA, A, VALENTI, V, RAGUSA, M, DITTA, M, SPINA, R, VIVONA, N, GIANGUZZA, F, NOTO, D, CEFALU, AB, NOTARBARTOLO, A, and AVERNA, MR
- Published
- 2007
10. PREVALENCE OF PCSK9 VARIANTS IN A COHORT OF SUBJECTS WITH HYPOCHOLESTEROLEMIA
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POLLACCIA, Daniela, VALENTI, Vincenza, CEFALU', Angelo Baldassare, BARRACO, Giacoma, FAYER, Francesca, MINA', Mariangela, BARBAGALLO, Carlo Maria, NOTARBARTOLO, Alberto, AVERNA, Maurizio, D. NOTO, P. TARUGI, S. CALANDRA, D POLLACCIA, V VALENTI, AB CEFALU', D NOTO, G BARRACO, F FAYER, M MINA', CM BARBAGALLO, A NOTARBARTOLO, P TARUGI, S CALANDRA, and AVERNA MR
- Published
- 2006
11. A NOVEL LOSS OF FUNCTION MUTATION OF PCSK9 GENE
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Fasano, T, Bocchi, L, Di leo, E, Cefalù, B, Noto, D, Valenti, V, Guardamagna, Ornella, Calandra, S, Averna, M, Tarugi, P., FASANO T, BOCCHI L, DI LEO E, CEFALU' AB, NOTO D, VALENTI V, GUARDAMAGNA O, CALANDRA S, AVERNA MR, and TARUGI P
- Subjects
LDLR gene ,PCSK9 gene ,loss of function ,missense mutation ,LDL-C ,hypocholesterolemic effect - Published
- 2006
12. VARIABLE PHENOTYPIC ESPRESSION IN A LIPID ABSORPTION DISORDER DUE TO A MOLECULAR DEFECT IN THE SARA2 GENE
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VALENTI, Vincenza, CEFALU', Angelo Baldassare, BALDI, Maria Elsa, POLLACCIA, Daniela, VIVONA, Nicoletta, BARBAGALLO, Carlo Maria, NOTARBARTOLO, Alberto, AVERNA, Maurizio, CALVO, PL, BARBERA, C, NOTO, D, VALENTI, V, CALVO, PL, CEFALU', AB, BALDI, M, POLLACCIA, D, BARBERA, C, VIVONA, N, NOTO, D, BARBAGALLO, CM, NOTARBARTOLO, A, and AVERNA, MR
- Published
- 2006
13. Prevalence and predictive role of hypertriglyceridemia in statin-treated patients at very high risk: Insights from the START study.
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De Luca L, Temporelli PL, Gulizia MM, Gonzini L, Ammaturo TA, Tedesco L, Pede S, Oliva F, Gabrielli D, Colivicchi F, and Averna MR
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- Humans, Cholesterol, LDL, Prevalence, Triglycerides, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hypertriglyceridemia diagnosis, Hypertriglyceridemia drug therapy, Hypertriglyceridemia epidemiology
- Abstract
Background and Aim: Elevated triglyceride (TG) levels seem to identify subjects at increased cardiovascular risk, independent of LDL-C levels. We sought to evaluate the predictive role of hypertriglyceridemia, defined as TG levels ≥150 mg/dl, in very high risk (VHR) patients with chronic coronary syndromes (CCS) treated with statins., Methods and Results: Using the data from the STable Coronary Artery Diseases RegisTry (START) study, an Italian nationwide registry, we assessed the association between the TG levels and baseline clinical characteristics, pharmacological treatment and major adverse cardio-cerebrovascular events (MACCE) at 1 year in a large cohort of statin-treated patients at VHR. Of the 4751 consecutive patients with CCS enrolled in the registry and classified as VHR, 2652 (55.8%) had TG values available (mean 120.6 ± 54.9) and were treated with at least a statin at baseline: 2019 (76.1%) with TG < 150 and 633 (23.9%) with TG ≥ 150 mg/dl. At 1 year from enrolment, MACCE occurred in 168 (6.3%) patients, without differences between the two groups of TG (5.9 vs 7.6%; p = 0.14). At multivariable analysis, hypertriglyceridemia did not result as independent predictor of the MACCE (hazard ratio: 1.16; 95% confidence intervals: 0.82-1.64; p = 0.42)., Conclusions: In the present large, nationwide cohort of consecutive CCS patients at VHR with statin-controlled LDL-C levels, hypertriglyceridemia was present in around 24% of cases and did not result as predictor of MACCE at 1 year. Further studies with a longer follow-up and larger sample size are needed to better define the prognostic role of TG levels when intensive LDL lowering therapies are used., Competing Interests: Declaration of competing interest All authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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14. Comparison of two polygenic risk scores to identify non-monogenic primary hypocholesterolemias in a large cohort of Italian hypocholesterolemic subjects.
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Cefalù AB, Spina R, Noto D, Rabacchi C, Giammanco A, Simone ML, Brucato F, Scrimali C, Gueli-Alletti MG, Barbagallo CM, Tarugi P, and Averna MR
- Subjects
- Angiopoietin-Like Protein 3 genetics, Apolipoproteins B genetics, Cholesterol, LDL blood, Humans, Monomeric GTP-Binding Proteins genetics, Multifactorial Inheritance, Mutation, Proprotein Convertase 9 genetics, Risk Factors, Hypobetalipoproteinemias genetics, Lipid Metabolism Disorders genetics
- Abstract
Background: Primary Hypobetalipoproteinemias (HBL) are a group of dominant and recessive monogenic genetic disorders caused by mutations in APOB, PCSK9, ANGPTL3, MTTP, Sar1b genes and characterized by plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5
th percentile of the distribution in a given population. Mutations in the candidate genes account only for a small proportion of subjects with HBL suggesting a role for a polygenic contribution to the low cholesterol phenotype., Objective: To explore the complex genetic architecture of HBL we compared two polygenic risk scores in order to assess the role of the polygenic burden and the differences in the clinical phenotype between monogenic and polygenic HBL; we studied a cohort of 170 subjects with primary HBL referred over a 25-year period to 2 Italian reference centers have been studied., Methods: The genetic analyses have been based on: Sanger sequencing, in-house NGS customized panel and two scores, PRS1 and PRS2 for the polygenic burden., Results: Sixty 60 (35%) and 63 (37%) subjects had a monogenic and polygenic HBL respectively. LDL-C plasma levels were significantly lower in monogenic HBL (30.87 ± 3.12 mg/dl) compared with the non-monogenic HBL (42.80 ± 2.18 mg/dl) (p<0.002) with no differences in the percentage of fatty liver., Conclusion: Only PRS1 is effective in detecting polygenic HBL while PRS2 does not improve the polygenic diagnosis., (Copyright © 2022. Published by Elsevier Inc.)- Published
- 2022
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15. rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography.
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Noto D, Cefalù AB, Martinelli N, Giammanco A, Spina R, Barbagallo CM, Caruso M, Novo S, Sarullo F, Pernice V, Brucato F, Ingrassia V, Fayer F, Altieri GI, Scrimali C, Misiano G, Olivieri O, Girelli D, and Averna MR
- Subjects
- Age Factors, Aged, Biomarkers blood, Coronary Stenosis blood, Coronary Stenosis epidemiology, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Italy epidemiology, Lipids blood, Male, Middle Aged, Phenotype, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, Severity of Illness Index, Time Factors, Cadherins genetics, Coronary Angiography, Coronary Stenosis diagnostic imaging, Coronary Stenosis genetics, Polymorphism, Single Nucleotide
- Abstract
Background and Aims: Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients., Methods and Results: The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG. The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04-1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04-1.96) and 1.39 (1.22-1.58) respectively]., Conclusions: rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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16. PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study.
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Valenti V, Noto D, Giammanco A, Fayer F, Spina R, Altieri GI, Ingrassia V, Scrimali C, Barbagallo CM, Brucato F, Misiano G, Cefalù AB, and Averna MR
- Subjects
- Cells, Cultured, Humans, Mutation, Proprotein Convertase 9 genetics, Epidermal Growth Factor pharmacology, PCSK9 Inhibitors, Proprotein Convertase 9 physiology, Receptors, LDL metabolism
- Abstract
Background and Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradation in vitro., Methods: Huh7 human hepatoma cells were transiently transfected to overexpress the gain-of-function D374Y PCSK9 mutation, which has been associated with severe hypercholesterolemia in humans., Results: Transient transfection of cells with PCSK9-D374Y expression vector very effectively enhanced degradation of mature LDLR in Huh7. Treatment with both EGF-A and EGF-A truncated peptides inhibited this effect and showed increased LDLR protein in Huh7 cells transfected with PCSK9-D374Y in a clear concentration dependent manner. Huh7 transfected cells treated with increasing concentration of EGF-A analogs also showed an increase internalization of labeled Dil-LDL., Conclusions: The result of our study shows that EGF-A analogs are able to effectively hamper the enhanced degradation of LDLR in liver cells expressing PCSK9-D374Y., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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17. Withdrawal: Lipase maturation factor 1 is required for endothelial lipase activity.
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Ben-Zeev O, Hosseini M, Lai CM, Ehrhardt N, Wong H, Cefalù AB, Noto D, Averna MR, Doolittle MH, and Péterfy M
- Published
- 2019
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18. Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred.
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Spina R, Noto D, Barbagallo CM, Monastero R, Ingrassia V, Valenti V, Baschi R, Pipitone A, Giammanco A, La Spada MP, Misiano G, Scrimali C, Cefalù AB, and Averna MR
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Child, Female, Genotype, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Hypercholesterolemia epidemiology, Hypercholesterolemia genetics, Male, Middle Aged, N-Glycosyl Hydrolases genetics, Receptors, LDL metabolism, Sequence Analysis, DNA, Sicily epidemiology, Young Adult, Hyperlipoproteinemia Type III, Adaptor Proteins, Signal Transducing genetics, Hypercholesterolemia diagnosis
- Abstract
Background: Autosomal recessive hypercholesterolemia (ARH) is a rare inherited lipid disorder. In Sardinia, differently from other world regions, the mutated allele frequency is high. It is caused by mutations in the low-density lipoprotein receptor adaptor protein 1 gene. Fourteen different mutations have been reported so far; in Sardinia, 2 alleles (ARH1 and ARH2) explain most of the cases. Four ARH patients, all carriers of the ARH1 mutation, have been identified in mainland Italy and 2 in Sicily., Objective: The objectives of the study were to improve the molecular diagnosis of familial hypercholesterolemia (FH) and to estimate the frequency of the ARH1 allele in 2 free-living Sicilian populations., Methods: We sequenced by targeted next-generation sequencing 20 genes related to low-density lipoprotein metabolism in 50 hypercholesterolemic subjects. Subjects from 2 free-living populations from Northern (Ventimiglia Heart Study, 848 individuals) and Southern Sicily (Zabut Zabùt Aging Project, 1717 individuals) were genotyped for ARH1 allele., Results: We identified 1 homozygous carrier of the ARH1 mutation among the 50 hypercholesterolemic outpatients. Population-based genotyping of ARH1 in 2565 subjects allowed the identification of 1 heterozygous carrier. The overall estimated allele frequency of ARH1 in Sicily was 0.0002 (0.02%)., Conclusions: The identification of a new case of ARH in Sicily among 50 clinically diagnosed FH highlights the importance of next-generation sequencing analysis as tool to improve the FH diagnosis. Our results also indicate that ARH1 carrier status is present in ∼1:2500 of Sicilian inhabitants, confirming that ARH is extremely rare outside Sardinia., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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19. The role of registries in rare genetic lipid disorders: Review and introduction of the first global registry in lipoprotein lipase deficiency.
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Steinhagen-Thiessen E, Stroes E, Soran H, Johnson C, Moulin P, Iotti G, Zibellini M, Ossenkoppele B, Dippel M, and Averna MR
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- Genetic Predisposition to Disease, Humans, Hyperlipoproteinemia Type I diagnosis, Hyperlipoproteinemia Type I enzymology, Hyperlipoproteinemia Type I epidemiology, Lipid Metabolism, Inborn Errors diagnosis, Lipid Metabolism, Inborn Errors enzymology, Lipid Metabolism, Inborn Errors epidemiology, Phenotype, Prognosis, Rare Diseases diagnosis, Rare Diseases enzymology, Rare Diseases epidemiology, Risk Factors, Hyperlipoproteinemia Type I genetics, Lipid Metabolism, Inborn Errors genetics, Lipoprotein Lipase genetics, Rare Diseases genetics, Registries
- Abstract
A good understanding of the natural history of rare genetic lipid disorders is a pre-requisite for successful patient management. Disease registries have been helpful in this regard. Lipoprotein Lipase Deficiency (LPLD) is a rare, autosomal-recessive lipid disorder characterized by severe hypertriglyceridemia and a very high risk for recurrent acute pancreatitis, however, only limited data are available on its natural course. Alipogene tiparvovec (Glybera
® ) is the first gene therapy to receive Marketing Authorization in the European Union; GENIALL (GENetherapy In the MAnagement of Lipoprotein Lipase Deficiency), a 15-year registry focusing on LPLD was launched in 2014 as part of its Risk Management Plan. The aim of this publication is to introduce the GENIALL Registry within a structured literature review of registries in rare genetic lipid disorders. A total of 11 relevant initiatives/registries were identified (homozygous Familial Hypercholesterolemia (hoFH) [n = 5]; LPLD [n = 1]; Lysosomal Acid Lipase Deficiency [LALD, n = 1], detection of mutations in genetic lipid disorders [n = 4]). Besides one product registry in hoFH and the LALD registry, all other initiatives are local or country-specific. GENIALL is the first global prospective registry in LPLD that will collect physician and patient generated data on the natural course of LPLD, as well as long-term outcomes of gene therapy., Conclusion: There is a limited number of international initiatives focusing on the natural course of specific rare genetic lipid disorders. The GENIALL LPLD Registry could be the first step towards a future broader global initiative that collects data related to familial chylomicronemia syndrome and their underlying genetic causes., (Copyright © 2016. Published by Elsevier B.V.)- Published
- 2017
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20. Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing.
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Cefalù AB, Spina R, Noto D, Ingrassia V, Valenti V, Giammanco A, Fayer F, Misiano G, Cocorullo G, Scrimali C, Palesano O, Altieri GI, Ganci A, Barbagallo CM, and Averna MR
- Subjects
- Adult, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Phenotype, DNA Mutational Analysis, High-Throughput Nucleotide Sequencing, Hypertriglyceridemia genetics, Membrane Proteins genetics
- Abstract
Background: Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins., Objective: The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG., Methods: We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG>885 mg/dL-10 mmol/L): 4 positive controls in whom pathogenic mutations had previously been identified by Sanger sequencing and 7 patients in whom the molecular defect was still unknown., Results: The customized panel was accurate, and it allowed to confirm genetic variants previously identified in all positive controls with primary severe HTG. Only 1 patient of 7 with HTG was found to be carrier of a homozygous pathogenic mutation of the third novel mutation of LMF1 gene (c.1380C>G-p.Y460X). The clinical and molecular familial cascade screening allowed the identification of 2 additional affected siblings and 7 heterozygous carriers of the mutation., Conclusions: We showed that our targeted resequencing approach for genetic diagnosis of severe HTG appears to be accurate, less time consuming, and more economical compared with traditional Sanger resequencing. The identification of pathogenic mutations in candidate genes remains challenging and clinical resequencing should mainly intended for patients with strong clinical criteria for monogenic severe HTG., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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21. Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.
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Noto D, Cefalù AB, Barbagallo CM, Ganci A, Cavera G, Fayer F, Palesano O, Spina R, Valenti V, Altieri GI, Caldarella R, Giammanco A, Termini R, Burrascano M, Crupi G, Falletta A, Scafidi V, Sbordone D, La Seta F, and Averna MR
- Subjects
- Aged, Area Under Curve, Biomarkers blood, Blood Glucose metabolism, Cardiovascular Diseases diagnosis, Cardiovascular Diseases prevention & control, Chi-Square Distribution, Diet, Healthy, Diet, Mediterranean, Disease-Free Survival, Female, Humans, Incidence, Insulin Resistance, Italy epidemiology, Lipids blood, Male, Metabolic Syndrome blood, Metabolic Syndrome diagnosis, Middle Aged, Multivariate Analysis, Neoplasms diagnosis, Neoplasms prevention & control, Obesity diagnosis, Prevalence, Proportional Hazards Models, Protective Factors, ROC Curve, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Cardiovascular Diseases epidemiology, Metabolic Syndrome epidemiology, Neoplasms epidemiology, Obesity epidemiology
- Abstract
Background and Aims: Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity., Methods and Results: As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric hazards models. Best predictive threshold for metabolic parameters and metS criteria were recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0-2.4)] and the TG/HDL ratio (log
10 ) (Males > 0.225, Females > 0.272) [HR = 2.44 (1.3-4.4)] resulted independent predictors of survival free of cancer with a clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3-4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)]., Conclusions: Metabolic disturbances are predictive of cancer in a 25 years follow-up of a Mediterranean population following a traditional Mediterranean diet. The high prevalence of obesity and metS and the observed underlying condition of insulin resistance expose this population to an increased risk of cardiovascular disease and cancer despite the healthy nutritional habits., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)- Published
- 2016
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22. Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model.
- Author
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Noto D, Fayer F, Cefalù AB, Altieri I, Palesano O, Spina R, Valenti V, Pitrone M, Pizzolanti G, Barbagallo CM, Giordano C, and Averna MR
- Subjects
- Adult, Aged, Cholesterol Esters metabolism, Diet, Mediterranean, Female, Hep G2 Cells, Humans, Kinetics, Male, Middle Aged, Protein Binding, Sicily, Biomarkers blood, Carcinoma, Hepatocellular metabolism, Cholesterol, HDL blood, Heparan Sulfate Proteoglycans metabolism, Liver Neoplasms metabolism, Membrane Proteins metabolism, Myristic Acid blood
- Abstract
Background: HDL-C plasma levels are modulated by dietary fatty acid (FA), but studies investigating dietary supplementation in FA gave contrasting results. Saturated FA increased HDL-C levels only in some studies. Mono-unsaturated FA exerted a slight effect while poly-unsaturated FA mostly increased plasma HDL-C., Aims: This study presents two aims: i) to investigate the relationship between HDL-C levels and plasma FA composition in a Sicilian population following a "Mediterranean diet", ii) to investigate if FA that resulted correlated with plasma HDL-C levels in the population study and/or very abundant in the plasma were able to affect HDL catabolism in an "in vitro" model of cultured hepatoma cells (HepG2)., Results: plasma HDL-C levels in the population correlated negatively with myristic acid (C14:0, β = -0.24, p < 0.01), oleic acid (C18:1n9, β = -0.22, p < 0.01) and cis-11-Eicosenoic (C20:1n9, β = -0.19, p = 0.01) and positively with palmitoleic acid (C16:1, β = +0.19, p = 0.03). HepG2 cells were conditioned with FA before evaluating HDL binding kinetics, and only C14:0 increased HDL binding by a non-saturable pathway. After removal of heparan sulphate proteoglycans (HSPG) by heparinases HDL binding dropped by 29% only in C14:0 conditioned cells (p < 0.05). C14:0 showed also the highest internalization of HDL-derived cholesteryl esters (CE, +32% p = 0.01 vs. non-conditioned cells)., Conclusions: C14:0 was correlated with decreased plasma HDL-C levels in a Mediterranean population. C14:0 might reduce HDL-C levels by increasing HDL trapping to cell surface HSPG and CE stripping from bound HDL. Other mechanisms are to be investigated to explain the effects of other FA on HDL metabolism., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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23. The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial.
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Stefanutti C, Blom DJ, Averna MR, Meagher EA, Theron Hd, Marais AD, Hegele RA, Sirtori CR, Shah PK, Gaudet D, Vigna GB, Sachais BS, Di Giacomo S, du Plessis AM, Bloedon LT, Balser J, Rader DJ, and Cuchel M
- Subjects
- Adult, Anticholesteremic Agents adverse effects, Benzimidazoles adverse effects, Biomarkers blood, Blood Component Removal adverse effects, Combined Modality Therapy, Female, Genetic Predisposition to Disease, Humans, Hyperlipoproteinemia Type II blood, Hyperlipoproteinemia Type II diagnosis, Hyperlipoproteinemia Type II genetics, Lipoprotein(a) blood, Male, Phenotype, Time Factors, Treatment Outcome, Young Adult, Anticholesteremic Agents administration & dosage, Benzimidazoles administration & dosage, Blood Component Removal methods, Cholesterol, LDL blood, Homozygote, Hyperlipoproteinemia Type II therapy
- Abstract
Objective: Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide., Methods: Existing lipid-lowering therapy, including apheresis, was to remain stable from Week -6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide., Results: Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (-48%) and not treated (-55%) with apheresis (p = 0.545). Changes in Lp(a) levels were modest and not different between groups (p = 0.436)., Conclusion: The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
- Published
- 2015
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24. Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature.
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Cefalù AB, Norata GD, Ghiglioni DG, Noto D, Uboldi P, Garlaschelli K, Baragetti A, Spina R, Valenti V, Pederiva C, Riva E, Terracciano L, Zoja A, Grigore L, Averna MR, and Catapano AL
- Subjects
- Abetalipoproteinemia genetics, Adult, Alternative Splicing, Cholesterol blood, Cholesterol, LDL blood, DNA Mutational Analysis, Female, Humans, Infant, Introns, Male, Apolipoprotein B-100 genetics, Homozygote, Hypobetalipoproteinemias diagnosis, Hypobetalipoproteinemias genetics, Mutation
- Abstract
Objective: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5(th) percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL., Methods: A one month old infant with failure to thrive, severe hypocholesterolemia and acanthocytosis was clinically and genetically characterized. Molecular characterization of the proband and her parents was performed by direct sequencing of the APOB gene and functional role of the identified mutations was assessed by the minigene methodology., Results: The proband was found carrying two novel splicing mutations of the APOB gene (c.3696+1G > C and c.3697-1G > A). CHOK1H8 cells expressing minigenes harbouring the mutations showed that these two mutations were associated with the retention of intron 23 and skipping of exon 24, resulting in two truncated apoB fragments of approximate size of 26-28 % of ApoB-100 and the total absence of apoB., Conclusion: We describe the first case of Ho-FHBL due to two splicing mutations affecting both the donor and the acceptor splice sites of the same intron of the APOB gene occurring in the same patient. The clinical management of the proband is discussed and a review of the clinical and genetic features of the published Ho-FHBL cases is reported., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
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- 2015
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25. Oxidative status in nondiabetic middle-aged subjects with metabolic syndrome: preliminary data.
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Hopps E, Lo Presti R, Noto D, Averna MR, and Caimi G
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- Adult, Antioxidants analysis, Cholesterol, HDL blood, Enzyme-Linked Immunosorbent Assay, Female, Humans, Linear Models, Lipid Peroxidation, Male, Metabolic Syndrome blood, Middle Aged, Nitric Oxide analysis, Protein Carbonylation, Triglycerides blood, Metabolic Syndrome physiopathology, Oxidative Stress
- Published
- 2013
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26. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study.
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Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, Averna MR, Sirtori CR, Shah PK, Gaudet D, Stefanutti C, Vigna GB, Du Plessis AM, Propert KJ, Sasiela WJ, Bloedon LT, and Rader DJ
- Subjects
- Benzimidazoles adverse effects, Cholesterol, LDL blood, Female, Homozygote, Humans, Hyperlipoproteinemia Type II blood, Hyperlipoproteinemia Type II genetics, Male, Benzimidazoles therapeutic use, Carrier Proteins antagonists & inhibitors, Hyperlipoproteinemia Type II drug therapy
- Abstract
Background: Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in adults with this disease., Methods: We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model., Findings: 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p<0·0001). Levels of LDL cholesterol were lower than 2·6 mmol/L in eight patients at 26 weeks. Concentrations of LDL cholesterol remained reduced by 44% (95% CI -57 to -31; p<0·0001) at week 56 and 38% (-52 to -24; p<0·0001) at week 78. Gastrointestinal symptoms were the most common adverse event. Four patients had aminotransaminase levels of more than five times the upper limit of normal, which resolved after dose reduction or temporary interruption of lomitapide. No patient permanently discontinued treatment because of liver abnormalities., Interpretation: Our study suggests that treatment with lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia., Funding: FDA Office of the Orphan Product Development, Aegerion Pharmaceuticals., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2013
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27. Plasma non-cholesterol sterols in primary hypobetalipoproteinemia.
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Noto D, Cefalù AB, Barraco G, Fayer F, Minà M, Yue P, Tarugi P, Schonfeld G, and Averna MR
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- Absorption, Adolescent, Adult, Aged, Aged, 80 and over, Child, Cholesterol analogs & derivatives, Cholesterol blood, Cholesterol chemistry, Family Health, Humans, Intestinal Mucosa metabolism, Middle Aged, Models, Genetic, Mutation, Phenotype, Phytosterols blood, Hypobetalipoproteinemias blood, Sterols metabolism
- Abstract
Primary hypobetalipoproteinemia (pHBL) is characterized by plasma cholesterol levels <5th percentile of a population distribution. Plasma non-cholesterol sterols (NCS) are markers of cholesterol liver synthesis and intestinal absorption. Plasma NCS were measured in 111 pHBL subjects, 108 low cholesterol (LC) and 253 normal cholesterol (NC) controls to gain information on cholesterol metabolism in pHBL, and to assess whether NCS measurements may aid in distinguishing pHBL from LC controls. pHBL subjects compared with LC controls were characterized by increased cholesterol absorption (campesterol/TC) while the synthesis (lathosterol/TC) was not increased. The analysis of pHBL subjects divided by gene defect showed a high campesterol/TC ratio in familial HBL (FHBL) carriers of apolipoproteinB (ApoB) truncations longer than ApoB48 and in FHBL without known gene defect ("not linked"). One not linked kindred was characterized by an increase of the 7-dehydrocholesterol/latho ratio. In a discriminant analysis plasma NCS did not improve the power of TC levels to distinguish FHBL from LC controls. In conclusion, increased cholesterol absorption was found in FHBL subjects harbouring truncations of ApoB>ApoB48, and FHBL harbouring as yet unknown molecular defects. Not linked FHBL kindred are not homogeneous in terms of plasma NCS levels. NCS cannot replace genetic HBL analysis., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
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28. Lipase maturation factor 1 is required for endothelial lipase activity.
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Ben-Zeev O, Hosseini M, Lai CM, Ehrhardt N, Wong H, Cefalù AB, Noto D, Averna MR, Doolittle MH, and Péterfy M
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- Animals, Chromatography, Affinity, Electroporation, Endoplasmic Reticulum genetics, Fibroblasts cytology, HEK293 Cells, Humans, Hypertriglyceridemia genetics, Hypertriglyceridemia physiopathology, Lipase genetics, Lipoprotein Lipase genetics, Mice, Mutation, Plasmids, Transfection, Endoplasmic Reticulum metabolism, Fibroblasts metabolism, Hypertriglyceridemia metabolism, Lipase metabolism, Lipoprotein Lipase metabolism, Membrane Proteins genetics, Membrane Proteins metabolism
- Abstract
Lipase maturation factor 1 (Lmf1) is an endoplasmic reticulum (ER) membrane protein involved in the posttranslational folding and/or assembly of lipoprotein lipase (LPL) and hepatic lipase (HL) into active enzymes. Mutations in Lmf1 are associated with diminished LPL and HL activities ("combined lipase deficiency") and result in severe hypertriglyceridemia in mice as well as in human subjects. Here, we investigate whether endothelial lipase (EL) also requires Lmf1 to attain enzymatic activity. We demonstrate that cells harboring a (cld) loss-of-function mutation in the Lmf1 gene are unable to generate active EL, but they regain this capacity after reconstitution with the Lmf1 wild type. Furthermore, we show that cellular EL copurifies with Lmf1, indicating their physical interaction in the ER. Finally, we determined that post-heparin phospholipase activity in a patient with the LMF1(W464X) mutation is reduced by more than 95% compared with that in controls. Thus, our study indicates that EL is critically dependent on Lmf1 for its maturation in the ER and demonstrates that Lmf1 is a required factor for all three vascular lipases, LPL, HL, and EL.
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- 2011
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29. A novel component of the metabolic syndrome: the oxidative stress.
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Hopps E, Noto D, Caimi G, and Averna MR
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- Animals, Cardiovascular Diseases complications, Diabetes Mellitus, Type 2 complications, Dyslipidemias complications, Humans, Hypertension complications, Inflammation complications, Metabolic Syndrome complications, Metabolic Syndrome diagnosis, Obesity, Abdominal complications, Risk Factors, Metabolic Syndrome physiopathology, Oxidative Stress
- Abstract
The metabolic syndrome (MS) represents a cluster of cardiovascular (CV) risk factors associated to CV disease and type 2 diabetes. It is still under debate whether MS is a mere aggregation of risk factors or it represents a clinical entity with visceral obesity as underlying pathophysiological trigger. The publication of several diagnostic criteria of MS by scientific associations or experts panels reflects this uncertainty in understanding the real nature of MS. Besides the metabolic disturbances of MS, as visceral obesity, hypertriglyceridemia, low HDL cholesterol, hypertension and hyperglycemia, novel mechanisms of arterial damage have been identified. This paper reviews the evidence showing that MS and MS factors are characterized by increased oxidative stress, a relevant factor contributing to the development of metabolic and cardiovascular complications. In the next future, the measure of plasma oxidative stress may contribute to identify a subset of MS patients at increased CV risk, candidates to more intensive therapies., (Copyright 2009 Elsevier B.V. All rights reserved.)
- Published
- 2010
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30. Hypertension and diabetes mellitus are associated with cardiovascular events in the elderly without cardiovascular disease. Results of a 15-year follow-up in a Mediterranean population.
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Noto D, Cefalù AB, Barbagallo CM, Sapienza M, Cavera G, Nardi I, Pagano M, Vivona N, Notarbartolo A, and Averna MR
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- Aged, Aged, 80 and over, Cardiovascular Diseases blood, Cardiovascular Diseases etiology, Cardiovascular Diseases mortality, Diabetes Complications, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 mortality, Female, Follow-Up Studies, Humans, Hypertension blood, Hypertension mortality, Incidence, Inflammation blood, Italy epidemiology, Lipids blood, Male, Risk Factors, Survival Analysis, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 epidemiology, Hypertension epidemiology
- Abstract
Background and Aims: Epidemiological prospective data on cardiovascular (CV) events in elderly subjects from Mediterranean populations are lacking. We aimed to investigate 15-year incidence of CV events and to evaluate the association with CV risk factors in an elderly Mediterranean population., Methods and Results: The population of a small Sicilian village were enrolled, visited and a blood sample was drawn at baseline. CV events were recorded in the 15 years of follow-up. From 1351 subjects (75% of the resident population); 315 were in the age range 65-85 years; 266 subjects free from CV disease were analysed. Seventy-seven CV events were recorded in 73 out of 266 subjects, with a 19.7% rate (in 10 years). Hypertension (HTN) (hazards ratio=2.1) and diabetes mellitus (DM) (hazards ratio=1.8) were independently associated with CV events. Subjects with both DM and HTN showed a lower survival free of CV events compared to those with DM or HTN., Conclusions: In a 15-year follow-up of an elderly Mediterranean population free from CV disease, diabetes mellitus and hypertension were related to CV events. The control of risk factors in the elderly needs to be reinforced to achieve better results in terms of CV prevention.
- Published
- 2009
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31. Novel mutations of CETP gene in Italian subjects with hyperalphalipoproteinemia.
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Cefalù AB, Noto D, Magnolo L, Pinotti E, Gomaraschi M, Martini S, Vigna GB, Calabresi L, Tarugi P, and Averna MR
- Subjects
- Adolescent, Adult, Aged, Animals, Biomarkers blood, COS Cells, Chlorocebus aethiops, Cholesterol Ester Transfer Proteins blood, Cholesterol Ester Transfer Proteins deficiency, Cholesterol, HDL blood, DNA Mutational Analysis, Female, Humans, Hyperlipoproteinemias blood, Hyperlipoproteinemias enzymology, Hyperlipoproteinemias ethnology, Italy, Male, Middle Aged, Phenotype, RNA, Messenger metabolism, Transfection, Up-Regulation, Young Adult, Cholesterol Ester Transfer Proteins genetics, Hyperlipoproteinemias genetics, Mutation, White People genetics
- Abstract
Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyses the transfer of cholesteryl esters from HDL to the other plasma lipoproteins. Genetic deficiency of CETP is one of the known causes of elevation of plasma HDL-C (primary hyperalphalipoproteinemia, HALP). We sequenced CETP gene in a group of 24 Italian subjects with primary HALP (HDL-C>80 mg/dl) suspected to have CETP deficiency. Two unrelated subjects both coming from the same geographical district, were found to be heterozygous for a nucleotide substitution in exon 6 (c.544C>T) and another subject was found to be heterozygous for a C>T transition in exon 9 (c.802C>T). Both mutations introduce a premature stop codon and are predicted to cause the production of truncated proteins (Q165X and R268X, respectively) devoid of function. The fourth proband was found to carry a T>C substitution in intron 15 (c.1407+2T>C) predicted to abolish the function of the donor splice site. To define the effect of this mutation on CETP pre-mRNA splicing we analysed CETP mRNA in COS-1 cells expressing a CETP minigene harbouring the mutation. The analysis of minigene transcript in COS-1 cells showed that IVS15+2T>C mutation caused the formation of an abnormal mRNA in which exon 14 joins directly to exon 16, predicted to encode a truncated peptide of 435 amino acids. In mutation carriers plasma CETP activity was found to be reduced by 38-60%. These are the first mutations in the CETP gene found in Italian subjects with HALP.
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- 2009
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32. The metabolic syndrome predicts cardiovascular events in subjects with normal fasting glucose: results of a 15 years follow-up in a Mediterranean population.
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Noto D, Barbagallo CM, Cefalù AB, Falletta A, Sapienza M, Cavera G, Amato S, Pagano M, Maggiore M, Carroccio A, Notarbartolo A, and Averna MR
- Subjects
- Adult, Aged, Angina Pectoris epidemiology, Blood Glucose, Coronary Artery Disease epidemiology, Diabetes Mellitus epidemiology, Fasting, Female, Follow-Up Studies, Humans, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction epidemiology, Obesity epidemiology, Predictive Value of Tests, Prevalence, Prospective Studies, Risk Factors, Sicily epidemiology, Stroke epidemiology, Cardiovascular Diseases epidemiology, Glucose Intolerance epidemiology, Metabolic Syndrome epidemiology
- Abstract
Unlabelled: The aim of this study was to evaluate the cardiovascular (CV) risk due to the metabolic syndrome in a 15-year prospective study of a Sicilian population. In the Mediterranean area obesity is highly prevalent, but epidemiological data on the metabolic syndrome are limited., Methods and Results: Among the 1351 subjects enrolled in the "Ventimiglia di Sicilia" epidemiological project, we selected 687 subjects between 35 and 75 years of age; baseline parameters were assessed and subjects have been followed for 15 years recording CV events, total and cardiovascular mortality. The metabolic syndrome was defined according to both the Adult Treatment Panel III and the International Diabetes Federation criteria. Metabolic syndrome (ATPIII criteria) was significantly (p<0.00001) more prevalent in women (31.5%) than in men (12.4%). The metabolic syndrome increased the risk of CV events with a hazard ratio of 1.9 (confidence interval CI; 1.46-2.46). Using a Cox proportional hazards estimation model, the survival curve of subjects with metabolic syndrome and normal fasting glucose did not significantly differ from the curve of subjects with metabolic syndrome and impaired fasting glucose (IFG)., Conclusions: In a 15-year follow-up the metabolic syndrome is predictive of CV events regardless of the presence of IFG or diabetes mellitus.
- Published
- 2008
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33. Family history, diabetes and extension of coronary atherosclerosis are strong predictors of adverse events after PTCA: A one-year follow-up study.
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Rizzo M, Barbagallo CM, Noto D, Pace A, Cefalú AB, Pernice V, Pinto V, Rubino A, Pieri D, Traina M, Frasheri A, Notarbartolo A, and Averna MR
- Subjects
- Aged, Analysis of Variance, Body Mass Index, Cholesterol, HDL blood, Coronary Angiography, Coronary Artery Disease surgery, Diabetes Complications, Diabetes Mellitus genetics, Female, Humans, Logistic Models, Male, Middle Aged, Obesity epidemiology, Prognosis, Prospective Studies, Sex Characteristics, Angioplasty, Balloon, Coronary, Coronary Artery Disease genetics, Coronary Artery Disease mortality, Diabetes Mellitus epidemiology, Treatment Outcome
- Abstract
Background and Aim: In this study we addressed some open questions in patients with coronary artery disease (CAD). First, we analysed which of the traditional risk factors was associated with the spreading of coronary stenosis and second, we aimed to identify if any variable was predictive of post-percutaneous transluminal coronary angioplasty (PTCA) clinical events., Methods and Results: We collected a consecutive series of patients with CAD (n=301) and in the subgroup of patients undergoing PTCA (n=135) we performed a prospective one-year follow-up study recording cardiovascular morbidity and total mortality. According to the extension of coronary atherosclerosis, we found a significant relationship with the prevalence of diabetes in men and with plasma HDL-cholesterol concentrations in women. The follow-up was completed in 95% of patients; we did not document any death whereas clinical events were registered in 16% of patients. At univariate analysis, we found that patients with clinical events had a higher prevalence of family history of CAD (43% vs 14%, p<0.005), diabetes (52% vs 21%, p<0.005) and multivessel disease (52% vs 35%, p<0.05). Multivariate analysis (logistic regression) confirmed that family history of CAD (OR 4.6, 95% CI 1.7-12.8, p<0.005), diabetes (OR 4.0, 95% CI 1.5-10.6, p<0.01) and multivessel disease (OR 2.8, 95% CI 1.1-7.4, p<0.05) were the only variables predictive of clinical events., Conclusions: In this study, factors associated with the spreading of coronary stenosis were different according to the gender. Moreover, the presence of diabetes and multivessel disease had a negative impact on the long-term prognosis of patients undergoing PTCA. In addition, the family history of CAD represented in our study a strong predictor of clinical events. We suggest that in the management of post-PTCA patients, the role of individual baseline clinical characteristics must be taken into account and that subjects with a family history of premature CAD, diabetes and a wide extension of coronary disease represent those with the highest risk.
- Published
- 2005
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34. Gastrointestinal symptoms in infancy: a population-based prospective study.
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Iacono G, Merolla R, D'Amico D, Bonci E, Cavataio F, Di Prima L, Scalici C, Indinnimeo L, Averna MR, and Carroccio A
- Subjects
- Adult, Breast Feeding statistics & numerical data, Failure to Thrive epidemiology, Female, Follow-Up Studies, Gestational Age, Hospitalization statistics & numerical data, Humans, Infant, Infant Formula, Infant, Low Birth Weight, Infant, Newborn, Italy epidemiology, Male, Prospective Studies, Colic epidemiology, Constipation epidemiology, Diarrhea, Infantile epidemiology, Gastroesophageal Reflux epidemiology, Vomiting epidemiology
- Abstract
Background: During the first months of life, infants can suffer from many 'minor' gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset., Aims: (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms., Study Design and Patients: Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination., Results: 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breast-feeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles., Conclusions: Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a 'dietary' milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms.
- Published
- 2005
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35. Cystatin C levels are decreased in acute myocardial infarction: effect of cystatin C G73A gene polymorphism on plasma levels.
- Author
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Noto D, Cefalu' AB, Barbagallo CM, Pace A, Rizzo M, Marino G, Caldarella R, Castello A, Pernice V, Notarbartolo A, and Averna MR
- Subjects
- Aged, Case-Control Studies, Cholesterol blood, Cystatin C, Female, Humans, Male, Middle Aged, Polymorphism, Genetic genetics, Time Factors, Triglycerides blood, Angina, Unstable blood, Angina, Unstable genetics, Cystatins blood, Cystatins genetics, Myocardial Infarction blood, Myocardial Infarction genetics
- Abstract
Background: Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography., Methods: In this study, plasma levels of cystatin C have been investigated in patients with acute myocardial infarction (AMI), unstable angina and controls. The effect on plasma levels of the G73A polymorphism of the CST3 gene has been also evaluated., Results: Patients with acute myocardial infarction showed significantly lower levels of cystatin C compared to unstable angina and controls, but levels were nearly normal in a week after the acute event. The genotype distribution of the G73A polymorphism was not different among the groups. Nevertheless, cystatin C levels decreased proportionally with the number of A alleles. Cystatin C levels were positively correlated with age, triglyceride/HDL cholesterol ratio and creatinine, and negatively with HDL cholesterol and the number of A alleles. All variables, but not HDL cholesterol, were independently correlated in a multivariate analysis., Conclusions: Cystatin C is decreased in acute myocardial infarction. It is still not clear whether lower cystatin C levels are causally linked to the acute event or just represent a negative acute phase response. The CST3 gene G73A polymorphism functionally affects cystatin C plasma levels.
- Published
- 2005
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36. Two Italian kindreds carrying the Arg136-->Ser mutation of the Apo E gene: development of premature and severe atherosclerosis in the presence of epsilon 2 as second allele.
- Author
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Rolleri M, Vivona N, Emmanuele G, Cefalù AB, Pisciotta L, Guido V, Noto D, Fiore B, Barbagallo CM, Notarbartolo A, Travali S, Bertolini S, and Averna MR
- Subjects
- Alleles, Apolipoprotein E2, Arteriosclerosis etiology, Base Sequence, Female, Genotype, Haplotypes, Humans, Hyperlipoproteinemia Type III complications, Lipids blood, Male, Middle Aged, Mutation, Pedigree, Polymerase Chain Reaction, Sequence Homology, Apolipoproteins E genetics, Arteriosclerosis genetics, Hyperlipoproteinemia Type III genetics
- Abstract
Background and Aims: Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cys112, Cys158). Apo E2-Christchurch (Arg136-->Ser), a rare mutation of the Apo E gene, located in the receptor-binding domain of the protein, has been found to be associated in the vast majority of cases of dysbetalipoproteinemia., Methods and Results: This is the first report of two Italian kindreds carrying the Arg136-->Ser mutation. One family is a four-generation kindred from Genoa (Liguria, Italy) with a high rate of mortality due to coronary artery disease: the proband was a 51-year-old woman with previous myocardial infarction and residual angina, severe carotid atherosclerosis, peripheral arterial vascular disease and arterial hypertension. The other family was identified in Palermo (Sicily, Italy): the proband was an overweight 62-year-old man with a mixed form of hyperlipidemia. The mutation, which was identified by means of Apo E genotyping followed by direct sequencing, co-segregated with the same haplotype in the two families., Conclusions: The family histories and clinical examinations of these subjects clearly show that the Apo E Arg136-->Ser variant fully expresses a type III phenotype in association with a second allele coding for Apo E2, and only partially in association with a second allele coding for Apo E4.
- Published
- 2003
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37. Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene.
- Author
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Barbagallo CM, Emmanuele G, Cefalù AB, Fiore B, Noto D, Mazzarino MC, Pace A, Brogna A, Rizzo M, Corsini A, Notarbartolo A, Travali S, and Averna MR
- Subjects
- Adult, Base Sequence, Coronary Angiography, Coronary Stenosis complications, Coronary Stenosis diagnostic imaging, DNA Mutational Analysis, Female, Follow-Up Studies, Humans, Hyperlipoproteinemia Type II complications, Hyperlipoproteinemia Type II drug therapy, Hypolipidemic Agents therapeutic use, Male, Molecular Sequence Data, Pedigree, RNA, Messenger analysis, Risk Assessment, Siblings, Sicily, Treatment Outcome, Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport genetics, Coronary Stenosis genetics, Genes, Recessive genetics, Heterozygote, Hyperlipoproteinemia Type II genetics, Point Mutation
- Abstract
We describe a Sicilian family presenting a recessive form of hypercholesterolemia harboring a mutation of the autosomal recessive hypercholesterolemia (ARH) gene. In two of the three sibs, a 26-year-old male and a 22-year-old female, a severe hypercholesterolemia was diagnosed with very high levels of plasma cholesterol (15.9 and 12.2 mmol/l, respectively); tendon xanthomatas and xanthelasms were present and in the male proband was documented a diffuse coronary atherosclerotic disease with a rapid and fatal progression. Both the parents had normal or slightly increased levels of plasma cholesterol. All causes of secondary hypercholesterolemia were ruled out as well as an involvement of the LDL receptor or apoB genes. Beta-Sitosterol plasma levels were in the normal range. Cultured fibroblasts from skin biopsy from parents and the two probands displayed a normal ability to bind and degrade 125I-LDL. Direct sequencing of ARH gene demonstrated the presence of a 432insA mutation in homozygosis in the two probands; parents were heterozygotes for the same mutation. This mutation is the first report of a mutation of the ARH gene responsible for recessive forms of hypercholesterolemia in Sicily.
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- 2003
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38. Distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in a small Mediterranean island: the Ustica Project.
- Author
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Barbagallo CM, Polizzi F, Severino M, Onorato F, Noto D, Cefalù AB, Rizzo M, Notarbartolo A, and Averna MR
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases blood, Cardiovascular Diseases mortality, Diet, Mediterranean, Female, Humans, Hyperlipidemias blood, Hyperlipidemias mortality, Italy epidemiology, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Male, Mediterranean Islands epidemiology, Middle Aged, Obesity blood, Obesity complications, Risk Factors, Cardiovascular Diseases epidemiology, Hyperlipidemias epidemiology, Lipids blood, Lipoproteins blood, Obesity epidemiology
- Abstract
Background and Aim: The populations of the Mediterranean area have a low incidence of cardiovascular disease (CHD). The aims of this paper are: 1) to present demographic data of the population of Ustica, a small island in the southern part of the Tyrrhenian sea that has reduced communications with the mainland and a diet presumably rich in fish; and 2) to evaluate the distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in this population., Methods and Results: We invited all of the free-living resident population aged more than 14 years (about 800 individuals) to participate in the study; 576 responded, for a participation rate of about 73%. The distribution of cardiovascular risk factors, plasma lipids, lipoproteins and dyslipidemias were evaluated in all of the subjects. More than 60% of the population was out of the normal weight range. Total and low-density lipoprotein cholesterol levels were respectively 207.4 +/- 46.7 and 141.7 +/- 42.4 mg/dL, and similar in males and females. Lipoprotein (a) (Lp[a]) levels presented the classical "skewed" distribution and, among the apolipoprotein(a) isoforms, there was a clear predominance of intermediate-sized kringle IV repeats. Overall, 43% of the subjects had a lipid disorder: the prevalence of hypercholesterolemia was 22.8% (3.2% with severe hypercholesterolemia terolemia > or = 300 mg/dL); low high-density lipoprotein cholesterol levels were found in 22.5%; the so-called lipid triad in 2.1%; and high Lp(a) levels in 6.2%. Large familial clusters were found for some lipid disorders., Conclusions: A large prevalence of body weight disturbances and high frequency of dyslipidemias are the main characteristics of this population. Ongoing data and future longitudinal studies will better clarify the relative influence of each parameter on CHD risk and total mortality.
- Published
- 2002
39. Effectiveness of screening for known mutations in Sicilian patients with "probable" familial hypercholesterolemia.
- Author
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Cefalù AB, Emmanuele G, Marino G, Fiore B, Caldarella R, Vivona N, Noto D, Barbagallo CM, Costa S, Gueli MC, Bertolini S, Notarbartolo A, Travali S, and Averna MR
- Subjects
- Cohort Studies, Exons, Gene Frequency, Genetic Testing economics, Humans, Hyperlipoproteinemia Type II diagnosis, Hyperlipoproteinemia Type II etiology, Mutation, Polymerase Chain Reaction, Sicily, Hyperlipoproteinemia Type II genetics, Receptors, LDL genetics
- Abstract
Background and Aim: More than 750 mutations in the low-density lipoprotein (LDL) receptor gene are currently known to cause familial hypercholesterolemia (FH), but the array of mutations varies considerably in different populations. The definition of essentially all the LDL receptor gene mutations in a population is therefore a prerequisite for the implementation of nation-wide genetic testing for FH., Methods and Results: In this study, a screening strategy based on PCR-enzymatic digestion and PCR-allele specific hybridisation procedures was used to evaluate the frequency distributions of 11 known mutations in a cohort of 214 unrelated subjects meeting the diagnostic criteria of "probable" FH. We identified 20 mutation carriers (9.3%). One mutation (FH Palermo-1) occurred with a relatively high frequency, accounting for 7% of the entire study cohort. We also report the first observation of the receptor-negative mutation V408M (Afrikaner-2) in Italy., Conclusions: Our screening approach is not effective and, at least in our area, it is not a suitable alternative to the more expensive and time-consuming sequencing approach. However, our data suggest that it is possible to identify the molecular defect in about 10% of Sicilian patients with a clinical diagnosis of "probable FH" using a rapid laboratory diagnostic mutation panel. Four mutations were responsible for all of the diagnosed cases, and it could be reasonable to use this 4-mutation panel as a preliminary step before adopting a more complex laboratory approach.
- Published
- 2001
40. Leukocyte count, diabetes mellitus and age are strong predictors of stroke in a rural population in southern Italy: an 8-year follow-up.
- Author
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Noto D, Barbagallo CM, Cavera G, Cefalu' AB, Caimi G, Marino G, Lo Coco L, Caldarella R, Notarbartolo A, and Averna MR
- Subjects
- Adult, Age Factors, Diabetes Complications, Female, Follow-Up Studies, Humans, Italy epidemiology, Leukocyte Count, Male, Middle Aged, Predictive Value of Tests, Rural Population, Stroke epidemiology, Stroke etiology
- Abstract
Stroke incidence rates in the Mediterranean area are higher compared to northern European countries. In this study, we present the 8-year prospective data from a small rural Sicilian town. This population, consisting of 1351 subjects (622 males and 729 females), is homogeneous for ethnic background with traditional healthy dietary habits and shows low cholesterol mean levels. We found that the risk of stroke was significantly associated with the record of at least one previous neurological symptom (PNS), such as lack of strength, loss of vision or speech or possible drop attacks, and high hematocrit in males, and to high body mass index (BMI) and waist-hip ratio (WHR), diabetes, hypertension, high leukocyte count in females. We also documented age-related differences: stroke was associated in younger subjects (age<65 years) with diabetes, high BMI, high uric acid levels and in older patients (age>/=65 years) with high WHR, hypertension, diabetes, PNS, leukocyte count and hematocrit above the 95th percentile. Multivariate analysis demonstrated an independent association between stroke and age, diabetes, leukocyte count, hypertension and PNS. In conclusion, in this rural Sicilian population, the incidence rate of stroke is 1.72 cases per 1000/year in the subjects between 40 and 75 years of age. The risk factors associated with stroke are different in younger and older subjects. Leukocyte count, as an expression of an undergoing inflammatory process, may have a relevant role at least in the elderly.
- Published
- 2001
- Full Text
- View/download PDF
41. Carotid atherosclerosis in hypercholesterolemic patients: relationship with cardiovascular events.
- Author
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Parrinello G, Barbagallo CM, Pinto A, Amato P, Cecala MG, Noto D, Cefalù AB, Scalisi G, Notarbartolo A, Averna MR, and Licata G
- Subjects
- Age Factors, Carotid Artery Diseases blood, Carotid Artery Diseases epidemiology, Carotid Artery, Common diagnostic imaging, Cholesterol blood, Female, Follow-Up Studies, Humans, Hypertension complications, Male, Middle Aged, Prevalence, Risk Factors, Triglycerides blood, Ultrasonography, Carotid Artery Diseases etiology, Carotid Artery, Common pathology, Hypercholesterolemia complications
- Abstract
Background and Aim: Extracranial cerebrovascular atherosclerosis is a common feature of hypercholesterolemia and carotid lesions are good predictors of cardiovascular events in the general population. Factors associated with the carotid damage of hypercholesterolemic patients and their relationships with the occurrence of clinical events are investigated in this study., Methods and Results: One hundred and seventeen cardiovascular event-free hypercholesterolemic subjects underwent a complete clinical examination to look for additional risk factors. A blood sample was collected for lipoprotein determination and an ultrasound high resolution B-mode imaging examination of the common carotid arteries was performed. Patients were treated according to the current guidelines during a 4-yr follow-up and all major cardiovascular events were recorded. The prevalence of subjects with increased intima-media thickness and plaque was 21.4% and 29.9% respectively, higher than in normolipidemic controls. Carotid lesions were significantly related to age, hypertension and LDL-cholesterol and HDL-cholesterol levels. The relative risk of developing a major clinical event was 3.92 (95% CI 1.54-9.95, p < 0.004) among categories of carotid status. At multivariate analysis, cardiovascular events were independently related to the diagnosis of familial hypercolesterolemia (FH), baseline carotid score and mean levels of LDL-cholesterol and HDL-cholesterol during the follow-up., Conclusions: Common risk factors cooperate with plasma lipoprotein levels in increasing the frequency of carotid lesions of hypercholesterolemic patients. Since such lesions are useful predictors of clinical events, B-mode ultrasound evaluation of the carotids should be routinely included in the management of these patients.
- Published
- 2001
42. Apolipoprotein B-38.9 does not associate with apo[a] and forms two distinct HDL density particle populations that are larger than HDL.
- Author
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Groenewegen WA, Averna MR, Pulai J, Krul ES, and Schonfeld G
- Subjects
- Aged, Amino Acid Sequence, Apolipoproteins B chemistry, Apolipoproteins B metabolism, Base Sequence, Centrifugation, Density Gradient, Chromatography, Gel, Gene Deletion, Humans, Lipoproteins, HDL chemistry, Male, Molecular Sequence Data, Pedigree, Recombinant Proteins metabolism, Apolipoproteins A metabolism, Apolipoproteins B genetics, Lipoproteins, HDL metabolism, Mutation, Particle Size
- Abstract
We have identified a new truncated apolipoprotein B (apoB) that provides insights into the interaction of apoB with apo[a] and with lipids. Both total and LDL-cholesterol were below the 5th percentile in the proband; Lp[a] was 28 mg/dl. Four other affected individuals were identified in this kindred. Immunoblotting of plasma apoB-containing lipoproteins with an anti-apoB monoclonal antibody revealed a major band for apoB-100 and a minor band with apparent M(r) 217 kDa. The apoB truncation is due to a -1 frameshift mutation, consisting of a cytosine deletion at cDNA position 5444, that results in the translation of 22 novel amino acids terminating at residue 1767. The mutation was confirmed in the affected subjects by allele-specific oligonucleotide (ASO) analysis. Gel filtration of whole plasma revealed that the minority of apoB-38.9 eluted with IDL- and LDL-sized particles, while the majority (approximately 60%) eluted between LDL and HDL. Lp[a] eluted between VLDL and LDL. Upon preparative density gradient ultracentrifugation (DGUC), the majority of the plasma apoB-38.9 (approximately 65%) floated at a density of 1.12 g/ml coincident with the major peak of HDL cholesterol. Lp[a] floated at a peak density of 1.08 g/ml between LDL and HDL. Immunoblots of the apoB-38.9-containing HDL density DGUC fractions subjected to nondenaturing gradient gel electrophoresis (GGE) demonstrated two apoB-38.9-containing particle populations with diameters of approximately 15 nm and approximately 18 nm, respectively. Lipoproteins of these sizes were also detected when whole plasma was subjected to GGE and immunoblotting. The 15-18 nm lipoproteins correspond to the gel filtration populations eluting between LDL and HDL. Lysine-Sepharose chromatography of plasma yielded retained products that contained apo[a] and apoB-100 but not apoB-38.9. Immunoprecipitation of whole plasma with monospecific polyclonal anti-human apo[a] showed apo[a] and apoB-100, but no apoB-38.9 to be present in precipitates. ApoB-100 and apoB-38.9 were present in supernates. In in vitro incubations, recombinant apo[a] formed complexes with apoB-100 but not with apoB-38.9-containing particles. Our results show that the apoB-38.9 protein can be found in a variety of lipoproteins; however, the majority of apoB-38.9-containing lipoproteins float at a density equivalent to HDL but are larger than HDL, being intermediate in size between apoB-100 LDL and HDL. The heterogeneity of apoB-38.9 lipoproteins may reflect their dual tissue source, i.e., liver and intestine, and the discordance between size and density indicates a disproportionately reduced association of lipids with apoB-38.9. Finally, our data suggest that apoB-38.9 is incapable of forming complexes with apo[a] in plasma.
- Published
- 1994
43. A new case of apo C-II deficiency with a nonsense mutation in the apo C-II gene.
- Author
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Zanelli T, Catapano AL, Averna MR, Barbagallo CM, Liotta A, Giardina FC, and Notarbartolo A
- Subjects
- Apolipoprotein C-II, Base Sequence, Child, Preschool, Cholesterol blood, Exons physiology, Humans, Hyperlipoproteinemia Type II genetics, Isoelectric Focusing, Lipoprotein Lipase blood, Male, Molecular Sequence Data, Mutation, Polymerase Chain Reaction, Sequence Analysis, DNA, Triglycerides blood, Apolipoproteins C deficiency, Apolipoproteins C genetics
- Abstract
The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction (PCR). The sequence analysis revealed a substitution of adenosine for cytosine at position 3,002 in exon 3, leading to the introduction of a premature stop codon (TAA) at a position corresponding to aminoacid 37 of mature apo C-II. This mutation creates a new Rsa I restriction enzyme site in the apo C-II gene. Amplification of DNA from family members by PCR and digestion with Rsa I established that the patient is a true homozygote for this mutation. The same nucleotide has been substituted for the mutation apo C-IIPadova and apo C-IIBari previously described in two kindreds from Italy. From these data we speculate that base pair 3,002 in the apo C-II gene may represent a hot spot for mutation.
- Published
- 1994
- Full Text
- View/download PDF
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