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Background Lipid management is the first line of treatment for decreasing the incidence of cardiovascular events in patients with coronary heart disease (CHD), and a variety of indicators are used to evaluate lipid management. This work analyses the differences in LDL-C and apoB for lipid management evaluation, as well as explores the feasibility of skin cholesterol as a marker that can be measured non-invasively for lipid management. Methods The prospective study enrolled 121 patients who had been diagnosed with acute coronary syndrome (ACS) at the department of emergency medicine of the First Affiliated Hospital of the USTC from May 2020 to January 2021, and the patients were grouped into Group I (n=53) and Group II (n=68) according to whether they had comorbid hyperlipidemia and/or diabetes mellitus. All patients were administered 10 mg/day of rosuvastatin and observed for 12 weeks. Lipid management was assessed on the basis of LDL-C and apoB, and linear correlation models were employed to assess the relationship between changes in these well accepted markers to that of changes in skin cholesterol. Results Out of 121 patients with ACS, 53 patients (43.80 %) had combined hyperlipidemia and/or diabetes mellitus (Group I), while 68 patients (56.20 %) did not (Group II). Cardiovascular events occur at earlier ages in patients with CHD who are comorbid for hyperlipidemia and/or diabetes (PPPP Conclusions Examination of changes in apoB levels give patients with low initial LDL-C more informative data on lipid management than LDL-C readings. In addition, non-invasive skin cholesterol measurements may have the potential to be used independently for lipid management evaluation.

Background Dyslipidemia is a predisposing factor for coronary heart disease (CHD). High-intensity statin therapy is recommended as secondary prevention. ABCB1 and SLCO1B1 genes influence the efficacy and safety of statins. Xinjiang is a multi-ethnic area; however, little is known about the prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in minority groups with CHD. Objective To measure levels of lipid and apolipoprotein and the prevalence of dyslipidemia and gene polymorphisms of ABCB1, SLCO1B1 in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe populations with CHD in Xinjiang. Methods This descriptive retrospective study compares lipid levels in ethnic groups using Kruskal-Wallis test or analysis of variance. The study compared gene polymorphisms and the prevalence of dyslipidemia among different ethnic groups using the chi-square test. The lipid profiles in plasma were measured before lipid-lowering therapy using commercially available kits. Genotyping of SLCO1B1 and ABCB1 variants was performed using sequencing by hybridization. Results A total of 2218 patients were successfully screened, including 1044 Han, 828 Uygur, 113 Kazak, 138 Hui, 39 Tatar, 36 Kirgiz, and 20 Sibe patients. The overall mean age was 61.8 ± 10.8 years, and 72.5% of participants were male. Dyslipidemia prevalence in these ethnic groups was 42.1, 49.8, 52.2, 40.6, 48.7, 41.7, and 45.0%, respectively. The prevalence of dyslipidemia, high total cholesterol (TC), high triglycerides (TG), and high low density lipoprotein cholesterol (LDL-C) differed significantly among the groups (P = 0.024; P < 0.001; P < 0.001; P < 0.001, respectively). For the Han group, high LDL-C, high TC, and high TG prevalence differed significantly by gender (P = 0.001, P = 0.022, P = 0.037, respectively). The prevalence of high TC, high TG, and low high density lipoprotein cholesterol (HDL-C) differed significantly by gender in the Uygur group (P = 0.006, P = 0.004, P < 0.001, respectively). The prevalence of high TC in Hui patients significantly differed by gender (P = 0.043). These findings suggest that polymorphisms in ABCB1 and C3435T differ significantly across ethnicities (P < 0.001). Conclusions The prevalences of dyslipidemia, high TC, high TG, and high LDL-C in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe CHD patients in Xinjiang differed concerning ethnicity. Ethnic, gender, and lifestyle were the key factors that affected the lipid levels of the population. The prevalence of polymorphisms of ABCB1 and C3435T significantly differed across ethnicities. These findings will aid the selection of precision lipid-lowering medications and prevention and treatment of CHD according to ethnicity in Xinjiang.

Background To assess the value of peptidoglycan recognition protein 2 (PGLYRP2) in assessing the disease activity and lipid metabolism in patients with systemic lupus erythematosus (SLE). Methods SLE patients with stable disease (n = 15), active lupus nephritis (LN) (n = 15) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (n = 15) admitted to Northern Jiangsu People’s Hospital (Jiangsu, China) in 2019–2020 were recruited. In addition, volunteers with matched age and sex (n = 15) were enrolled as controls. The level of PGLYRP2 in the serum and its expression in peripheral blood mononuclear cells (PBMCs) were measured. The link between PGLYRP2 level and clinical parameters (including lipid profile) was described. Results Serum PGLYRP2 level in SLE cases exceeded that in healthy volunteers (3938.56 ± 576.07 pg/mL), and significantly higher in active LN (5152.93 ± 446.13 pg/mL) and NP-SLE patients (5141.52 ± 579.61 pg/mL). As shown by quantitative real-time PCR results, the expression of PGLYRP2 in PBMCs of SLE patients with active LN and NP-SLE surpassed that in healthy volunteers (P P = 0.000). PGLYRP2 level positively correlated with SLEDAI of SLE patients (r = 0.5783, P P Conclusions Serum PGLYRP2 level significantly increases in SLE patients, and is positively correlated to SLEDAI. Moreover, serum PGLYRP2 level is correlated with renal damage parameters and the abnormal lipid profile of SLE. PGLYRP2 could be used to predict SLE activity, dyslipidemia and cardiovascular disease risks in SLE patients.

Background Hypertriglyceridemia has arisen as the third leading cause of acute pancreatitis. This study aimed at exploring the association between the severity of hypertriglyceridemia-induced pancreatitis (HTGP) and computed tomography (CT)-based body composition parameters and laboratory markers. Methods Laboratory and clinical parameters were collected from 242 patients with HTGP between 2017 and 2020. Severity of HTGP was evaluated by original or modified CT severity index. Body composition parameters such as area and radiodensity of muscle, subcutaneous adipose tissue and visceral adipose tissue were calculated by CT at the level of third lumbar vertebra. Parameters were compared between mild and moderately severe to severe HTGP. Uni-variate and multi-variate Logistic regression analyses were employed to assess the risk factors of the severity of HTGP. Results Seventy patients (28.9%) presented with mild HTGP. Body mass index, waist circumference and all CT-based body composition parameters differed between male and female patients. None was associated with the severity of HTGP, neither in males nor in females. Receiver operating characteristic curves showed that areas under the curves of apolipoprotein A-I and albumin to predict the severity of HTGP were 0.786 and 0.759, respectively (all P P = 0.004, OR = 3.362, 95%CI = 1.492–8.823) and apolipoprotein A-I (P 90 mg/L, P = 0.005, OR = 3.061, 95%CI = 1.407–6.659) and lipase (P = 0.033, OR = 2.283, 95%CI = 1.070–4.873) were risk factors of moderately severe to severe HTGP. Levels of albumin, apolipoprotein A-I, C-reactive protein and lipase were also associated with the length of hospital stay (all P P Conclusions Low serum albumin and apolipoprotein A-I, and high C-reactive protein and lipase upon admission were associated with a more severe type of HTGP and longer hospital stay for these patients. Albumin and apolipoprotein A-I may serve as novel biomarkers for the severity of HTGP. However, none of the body composition parameters was associated with the severity of HTGP.

Background Apolipoprotein E (ApoE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) regulate lipid metabolism. However, the relationship between genetic polymorphisms of APOE and SLCO1B1 and cerebral infarction (CI) remains unclear. Methods A total of 938 CI patients and 1028 control participants were included in the study. The rs429358 and rs7412 single nucleotide polymorphisms (SNPs) in the APOE gene and rs2306283 and rs4149056 SNPs in the SLCO1B1 gene were analyzed by fluorescence polymerase chain reaction (PCR). Results The genotype ɛ3/ɛ3 was the most common APOE genotype, with ɛ3 being the allele with the highest frequency, followed by ɛ4 and ɛ2. Statistically significant differences of genotype ɛ2/ɛ2 (χ2 = 3.866, P = 0.049), ɛ2/ɛ3 (χ2 = 20.030, P 2 = 16.960, P 2 = 4.786, P = 0.029) between CI patients and controls were detected. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. There was no statistically significant difference in the frequencies of SLCO1B1 genotypes and haplotypes among CI patients comparing with controls. Moreover, ε4 carriers had significantly higher low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo-B) and lower apolipoprotein A1 (Apo-A1)/Apo-B levels than ε2 and ε3 carriers, but ε2 carriers showed lower LDL-C and Apo-B and higher Apo-A1/Apo-B than ε3 and ε4 carriers. Further, logistic regression analysis revealed that high LDL-C, high ApoB, smoking, hypertension and the ε4 allele were risks for the presence of CI. Conclusions This study indicated that the APOE SNPs rs429358 and rs7412 may be associated with susceptibility to cerebral infarction in southern Chinese Hakka population.

Background Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL’s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function. Methods A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement. Results In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q Conclusion Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.

Background: This study aims to investigate the association of lipid ratios with intracranial atherosclerotic stenosis (ICAS) in a Chinese population.Methods: This cross-sectional study included 658 consecutive patients with ischemic stroke. Intracranial and extracranial arteries were evaluated for atherosclerotic stenosis using digital subtraction angiography or computed tomography angiography. Lipid ratios [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG)/HDL-C, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C)/HDL-C, remnant cholesterol (RC)/HDL-C, apolipoprotein B (apo B)/apolipoprotein A-I (apo A-I), and apo B/HDL-C] were calculated.Results: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/HDL-C and apo B/apo A-I ratios (all P Conclusion: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C apo B/HDL-C, and apo B/apo A-I ratios were significantly related to ICAS risk. Compared with the other variables tested, the apo B/apo A-I ratio appeared to be a better discriminator for identifying ICAS risk in stroke patients.

Background Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. Methods A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. Results In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). Conclusions These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients’ evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.

Background The functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. Methods Eighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E + C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E + C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using non-denaturing electrophoresis and anti-apoA-I western blotting. Results HDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6% of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8, 12.2 and 8.37% of plasma LCAT respectively for E + C-, E-C+ and E + C+). LCAT mass was lower in E + C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r = − 0.55, P = 0.017) and E-C- alpha 1 HDL (r = − 0.49, P = 0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r = 0.52, P = 0.025). Conclusions The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.

Background We previously identified the c.344G > A: p.(Arg115His) variant in the low-density lipoprotein receptor (LDLR) gene, which was interpreted as “conflicting interpretations of pathogenicity” in ClinVar, based on a genetic analysis of patients with familial hypercholesterolemia (FH). However, whether this variant affects the pathophysiology of FH remains unclear. Therefore, our aim was to annotate the c.344G > A: p.(Arg115His) variant in the LDLR gene in FH. We present 2 families harboring the c.344G > A: p.(Arg115His) variant in the LDLR gene. Methods Genetic analyses were performed for the coding regions and the exon-intron boundary sequence of the LDLR and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes in 2 FH families. Next, the family without pathogenic variants in the LDLR and PCSK9 genes was screened by whole-exome sequencing. Detailed clinical and biochemical data were gathered from family members. Results In one family, the index case had biallelic c.1567G > A: p.(Val523Met) and c.344G > A: p.(Arg115His) variants in the LDLR gene, while the sibling had only the c.1567G > A: p.(Val523Met) variant in the LDLR gene. There was no difference in the FH phenotype between the siblings. In another family, the index case and the sibling had no pathogenic variants in the LDLR, PCSK9, and apolipoprotein B (APOB) genes, but the sibling’s wife with nonFH had the c.344G > A: p.(Arg115His) variant in the LDLR gene. The sibling and his wife had 4 children, including an unaffected child and an affected child who had the c.344G > A: p.(Arg115His) variant in the LDLR gene. In addition, the allele frequency of the c.344G > A: p.(Arg115His) variant (0.0023–0.0043) in Japanese and East Asian populations is relatively high compared with that of the other LDLR pathogenic variants (0.0001–0.0008). Conclusions The c.344G > A: p.(Arg115His) variant in the LDLR gene is interpreted as benign in individuals with FH.

Background Recent studies showed that dyslipidemia could be a critical factor in the progression of cardiovascular disease in systemic lupus erythematosus (SLE). The aim of the present study was to describe the relationship between serum lipid profile and SLE disease activity in young female adults with SLE. Methods Seventy-one female subjects diagnosed with SLE aged 20~30 years were enrolled. Serum lipid profile including TC, TG, HDL-C, LDL-C, VLDL-C, Apo A, Apo B, and Apo E were evaluated between control and young female SLE patients. Univariate correlation analyses were performed to explore the correlation between serum lipid levels and SLE disease activity. Results Our results showed that TG and VLDL-C levels were significantly increased in young female SLE as compared to control, with TC, HDL-C, LDL-C, Apo A, and Apo B significantly reduced. Meanwhile, univariate correlation analyses showed negative correlations between SLE disease activity index and HDL-C, LDL-C, Apo A, and Apo B; with positive correlations between SLE disease activity index and TG and VLDL-C. Conclusion Serum lipid profile was significantly dysregulated in young female SLE patients. Moreover, SLE disease activity was correlated to the serum lipid levels, supporting the notion that the young patients with SLE might also have a higher risk of cardiovascular disease.

Background Overconditioned dairy cows are prone to greater insulin resistance in transition to successfully adapt to negative energy balance. The associations among body condition score (BCS), insulin resistance, lipid metabolism and oxidative stress in cows during late lactation with positive energy balance remain to be elucidated. Methods The objectives of this study were to investigate insulin sensitivity and oxidative status in late lactating dairy cows with different BCS but similar milk production, parity and days in milk. Forty-two multiparous Holstein cows were fed the same diet under the same management and divided into three groups based on BCS: low BCS (LBCS; BCS ≤ 2.75; n = 12), medium BCS (MBCS; 3.0 ≤ BCS ≤ 3.5; n = 15) or high BCS (HBCS; BCS ≥ 3.75; n = 15). Blood samples used for analysis of biochemical and hematological parameters were collected from the coccygeal vein at the end of experiment. Results The concentrations of insulin and nonesterified fatty acid were higher and the revised quantitative insulin sensitivity check index (RQUICKI) was lower in HBCS cows than in LBCS and MBCS cows. These results suggest that insulin resistance exacerbates lipolysis in HBCS cows. Serum concentrations of very low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B were lower in HBCS cows than in LBCS or MBCS cows. Although LBCS and MBCS cows had higher reactive oxygen species levels than did HBCS cows, the malondialdehyde concentration was not different among cows with different BCS. Ceruloplasmin activity was higher in MBCS and HBCS cows than in LBCS cows, but superoxide dismutase, glutathione peroxidase, and paraoxonase activities were not different among cows with different BCS. Despite the higher percentage of granulocytes in MBCS cows than in HBCS cows, no differences were found in leukocyte counts, red blood cell profiles and platelet profiles among the cows in the three groups. Conclusions Results of this study showed that compared with MBCS and LBCS cows, HBCS cows at late lactation stage may have accumulated more hepatic triacylglycerol and lower antioxidant potential due to greater insulin resistance.

Background Increased evidence has reported the association of genetic polymorphisms of Apolipoprotein E (APOE) with serum lipids. However, few studies have explored the combined effects of APOE, gender, and age. Methods A total of 1,419 middle-aged and elderly subjects were randomly selected and studied. The APOE genotypes and the serum lipids were detected. The effects of APOE, gender, and age on serum lipids were preliminarily observed in general. The subjects were then divided into the middle-aged group (40–64 years old) and the elderly group (≥ 65 years old), for both males and females, to explore the combined effects of the APOE, gender, and age on serum lipids. Finally, a multivariate logistic regression model was used to evaluate the associations between the APOE allele carriers and the at-risk levels of dyslipidemia. Results The serum TC, LDL-C, and ApoB in the ε2 carriers were lower than the ε3 carriers (all P < 0.05), and there was no significant difference in the ε4 carriers compared to the ε3 carriers in general (all P > 0.05). The serum LDL-C and ApoB of the ε2 carriers were lower than the noncarriers in the middle-aged and elderly males (all P < 0.05). The serum TC in the ε2 carriers was lower than the noncarriers only in middle-aged males (P < 0.05). As to the levels of serum HDL-C and ApoA1, the ε2 carriers were higher than the noncarriers in middle-aged females (all P < 0.05), and the ε4 carriers were lower than noncarriers in middle-aged males (P < 0.05). Especially, the serum TG in the ε4 carriers was significantly higher than the noncarriers in elderly females. The logistic regression analysis indicated that the ε2 carriers were less likely to have at-risk levels of high LDL-C in middle-aged and elderly males (all P < 0.05) versus low HDL-C in middle-aged females (P < 0.05). In contrast, the ε4 carriers were more likely to have at-risk levels of high TG in elderly females (P < 0.05). Conclusions The effects of the genetic polymorphisms of APOE on the serum lipids were both gender- and age-dependent in the middle-aged and elderly Chinese Fujian Han population.

Background Evidence suggests that proteins related to lipid metabolism, such as apolipoproteins, play an important role in the maintenance of normal vision. While several members of the apolipoprotein family are abundant in human aqueous humor (AH), their study remains difficult due to the AH’s small volume, low protein concentration, and the invasive nature of sample collection. In this study, we report the use of Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to discover associations between AH apolipoproteins and race, gender, and ocular structure in patients with and without primary open angle glaucoma (POAG). Methods AH samples were collected from 231 patients undergoing phacoemulsification or glaucoma incisional surgery at the Medical College of Georgia, Augusta University and subsequently analyzed via LC-MS/MS. The number of peptide spectrum matches (PSMs) for each protein was used as a semi-quantitative measure of relative protein levels. Parameters related to ocular structure were determined using Optical Coherence Tomography (OCT) and Heidelberg Retinal Tomography (HRT). These data sets were probed for relationships between apolipoprotein levels and POAG, demographics (gender and race), and ocular structure. Results A total of ten apolipoproteins were detected in the 231 collected AH samples, with six detected in 100% of the samples, one detected in almost 57% of the samples and three detected in less than 10% of the samples. The levels of APOA1, APOC3, and APOD were higher among POAG subjects. Stratification by gender and race revealed demographic-specific variations. The levels of five apolipoproteins (APOA1, APOA2, APOA4, APOC3, and APOD) were higher in female POAG patients, whereas no apolipoprotein levels were altered in male POAG patients. The levels of APOA1, APOA2, APOA4, and APOD were increased in glaucomatous African American patients, whereas APOE and APOH levels were decreased in glaucomatous Caucasian patients. We also found distinct associations between apolipoprotein levels and OCT and HRT parameters in patients with and without POAG. Conclusions The intra-population variation in apolipoprotein levels highlights the heterogeneity of glaucoma as a disease, suggesting the importance of personalized treatments. Gender and race-specific alterations may be associated with higher risks of POAG in females and members of the African American population.

Background Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. Methods NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. Results Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). Conclusions Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

Background Discordance of lipid parameters is closely associated with residual cardiovascular risk. This study investigated the discordance between non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C), and assessed arterial stiffness risk. Methods This study included a total of 402 middle-aged and elderly Northern Chinese individuals whose brachial-ankle pulse wave conduction velocity (baPWV), and clinical and biochemical data were measured. Arterial stiffness was defined by inclusion in the upper quartile of the baPWV. All participants were divided into four mutually exclusive concordance/discordance groups based on the lipid goal for high-risk populations, according to the 2019 European Society of Cardiology / European Atherosclerosis Society guidelines. Discordance was defined as LDL-C ≥ 1.81 mmol/L with non-HDL-C Results The mean age of the participants was 65.9 ± 13.0 years; 59.5% of the participants were male. The mean LDL-C was 2.41 ± 0.81 mmol/L, non-HDL-C: 3.06 ± 0.94 mmol/L, and apoB: 0.84 ± 0.21 mmol/L. LDL-C was observed to be discordant with non-HDL-C (20.1%) and apoB (30.8%). When stratified according to LDL-C levels, the baPWV was greater in those patients with higher non-HDL-C or apoB levels. In the adjusted logistic regression model, low LDL-C and high non-HDL-C or apoB discordance were also associated with the risk of arterial stiffness (OR: 13.412 and OR: 13.054, respectively). Conclusions There was discordance between LDL-C and non-HDL-C, or apoB in middle-aged and elderly Chinese individuals; this was associated with a higher risk of arterial stiffness. Non-HDL-C or apoB levels could be used to identify individuals who may benefit from more comprehensive lipid modification.

Study design This was a cross-sectional frequency-matched case–control study. Background and aim The serum lipid profile of lipoprotein(a) [Lp(a)] level and apolipoprotein B/apolipoprotein A1 ratio (Apo B/Apo A1) ratio were found to be more representative for serum lipid level and were recognized as the independent risk factors for various diseases. Although the blood levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were found to be associated with symptomatic intervertebral disk herniation (IDH), no studies to date have evaluated the association of Apo AI, Apo B, Lp(a), and Apo B/Apo AI levels with symptomatic IDH. This study aimed to assess the link between blood lipid levels and symptomatic IDH. Method The study included 1839 Chinese patients. Of these, 918 patients were diagnosed with IDH and enrolled in the experimental group. A control group of 921 patients underwent a physical examination during the same period. The serum lipid levels of TC, TG, LDL-C, HDL-C, Lp(a), Apo B, and Apo B/Apo AI were examined and analyzed. The control group comprised randomly selected patients who met the baseline levels of the aforementioned lipid molecules. Results Patients with IDH exhibited significantly higher TC, TG, LDL, Apo B, and Lp(a) levels than controls. The percentage of high TC, high TG, high LDL, high Apo B, and high Lp(a) were obviously higher in the IDH group than in the control group. However, hyperlipidemia had no relationship with the degenerated segment of the IDH (P = 0.201). The odds ratio (OR) for the incidence of IDH with elevated levels of LDL-C, TC, TG, Lp(a), Apo B, and Apo B/Apo AI was 1.583, 1.74, 1.62, 1.58, 1.49, and 1.39, respectively. The correlation analysis revealed the correlation between elevated LDL-C, TC, TG, Apo B, Lp(a), and incidence of IDH was significant (R2LDL = 0.017; R2TC = 0.004; R2TG = 0.015; R2Apo B = 0.004; R2Lp(a) = 0.021) (P Conclusion This study suggested that elevated levels of serum TC, TG, LDL, Apo B, Lp(a), and Apo B/Apo AI were associated with a higher risk of IDH. This study provided useful information to identify a population that might be at risk of developing IDH based on elevated lipid levels.

Background Hepatitis B virus (HBV) infection remains a global health issue associated with substantial morbidity and mortality. Serum apolipoprotein C3 (ApoC3) and apolipoprotein A5 (ApoA5) levels were decreased in chronic hepatitis B (CHB) patients, however the relationship between ApoC3 or ApoA5 and HBV DNA load remains elusive. Methods A total of 384 CHB patients including 194 HBsAg(+) HBeAg(−) and 190 HBsAg(+) HBeAg(+) and 154 healthy individuals were recruited in our study. Serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (Chol), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), high-density lipoproteins cholesterol (HDL-C), low-density lipoproteins cholesterol (LDL-C) and lipoprotein a (Lpa) were examined in an automatic biochemical analyzer. Apolipoprotein A5 (ApoA5) and apolipoprotein C3 (ApoC3) were detected via ELISA. Results Serum ApoA1, ApoB, ApoC3 and ApoA5 levels were reduced in CHB patients. In HBeAg(−) CHB patients, plasma ApoC3 levels were negatively associated with HBV DNA load (r = 0.219, P

Background Hyperlipidemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that Coenzyme Q10(CoQ10) protects against cardiac damage in vivo. The aim of this study was to investigate the possible protective effects of CoQ10 against cardiac damage in apolipoprotein E-deficient (ApoE−/−) mice. Methods Eight-week-old male C57BL/6 and ApoE−/− mice were randomly divided into four groups: C57BL/6 mice fed a normal diet (C57BL/6 group); C57BL/6 mice fed a normal diet + CoQ10 (C57BL/6 + CoQ10 group); ApoE−/− mice fed a high-fat diet (ApoE−/− HD group), and ApoE−/− mice fed a high-fat diet + CoQ10 (ApoE−/− HD + CoQ10 group). All groups were fed the different diets for 16 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at − 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. Results The metabolic parameters such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglycerides (TG) levels were lower in ApoE−/−HD + CoQ10 mice than in ApoE−/− HD mice. There were significant pathophysiological changes (H&E, PAS, Masson and CD68 staining) in ApoE−/− mice in the HD group compared with those in the HD + CoQ10 group. CoQ10 reduced HD-induced cardiac tissue damage via autophagy (p62 and LC3), as evidenced by immunoblotting, immunohistochemistry, and RT-qPCR. CoQ10 also inhibited inflammation (IL-6 and TNF-α) gene expression in ApoE−/− mice. Conclusions These results indicate that CoQ10 is a potential therapeutic target for cardiac damage caused by hyperlipidemia.

Background Standard lipid panel assays employing chemical/enzymatic methods measure total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), from which are calculated estimates of low-density lipoprotein cholesterol (LDL-C). These lipid measures are used universally to guide management of atherosclerotic cardiovascular disease risk. Apolipoprotein B (apoB) is generally acknowledged to be superior to LDL-C for lipid-lowering therapeutic decision-making, but apoB immunoassays are performed relatively infrequently due to the added analytic cost. The aim of this study was to develop and validate the performance of a rapid, high-throughput, reagent-less assay producing an “Extended Lipid Panel” (ELP) that includes apoB, using the Vantera® nuclear magnetic resonance (NMR) analyzer platform already deployed clinically for lipoprotein particle and other testing. Methods Partial least squares regression models, using as input a defined region of proton NMR spectra of plasma or serum, were created to simultaneously quantify TC, TG, HDL-C, and apoB. Large training sets (n > ~ 1000) of patient sera analyzed independently for lipids and apoB by chemical methods were employed to ensure prediction models reflect the wide lipid compositional diversity of the population. The analytical performance of the NMR ELP assay was comprehensively evaluated. Results Excellent agreement was demonstrated between chemically-measured and ELP assay values of TC, TG, HDL-C and apoB with correlation coefficients ranging from 0.980 to 0.997. Within-run precision studies measured using low, medium, and high level serum pools gave coefficients of variation for the 4 analytes ranging from 1.0 to 3.8% for the low, 1.0 to 1.7% for the medium, and 0.9 to 1.3% for the high pools. Corresponding values for within-lab precision over 20 days were 1.4 to 3.6%, 1.2 to 2.3%, and 1.0 to 1.9%, respectively. Independent testing at three sites over 5 days produced highly consistent assay results. No major interference was observed from 38 endogenous or exogenous substances tested. Conclusions Extensive assay performance evaluations validate that the NMR ELP assay is efficient, robust, and substantially equivalent to standard chemistry assays for the clinical measurement of lipids and apoB. Routine reporting of apoB alongside standard lipid measures could facilitate more widespread utilization of apoB for clinical decision-making.

Background Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. Methods This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. Results Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901–0.970, 98.5% sensitivity, 92.2% specificity, P Conclusions The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.

Background Rubus coreanus (R. coreanus) possesses properties that may decrease cholesterol levels. Methods The effects of unripe R. coreanus (uRC) consumption on low-density lipoprotein (LDL) and total cholesterol levels related to decreased circulating apolipoprotein (Apo) B and oxidized LDL levels were evaluated. This randomized, double-blind, placebo-controlled study included subjects with borderline-high cholesterol levels (between 200 and 239 mg/dL) who consumed one capsule daily containing 600 mg of freeze-dried uRC extract (n = 39) or the placebo (n = 38). Results After 12 weeks, the uRC group showed reductions of 21.23 ± 4.36 mg/dL in total cholesterol levels (P = 0.007) and 15.61 ± 4.16 mg/dL in LDL cholesterol levels (P = 0.032). In addition, significantly greater reductions in Apo B levels were observed in the uRC group (− 3.48 ± 3.40 mg/dL), but Apo B levels were increased in the placebo group (6.21 ± 2.84 mg/dL; P = 0.032). Furthermore, a remarkably lower oxidized LDL level was detected in the uRC group (57.76 ± 2.07 U/L) than in the placebo group (66.09 ± 3.47 U/L) after 12 weeks of consumption (P = 0.044). Conclusions Because of its cholesterol-lowering effect, uRC shows great promise as a therapeutic agent for subjects with borderline-high total blood cholesterol levels. Trial registration ClinicalTrials.gov Identifier: NCT03649620 (8/28/2018, retrospectively registered).

Background Androgen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters. Methods Sixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted. Results ADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55μg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p p p Conclusion Increase in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Background Increased apolipoprotein (apo) B level (hyperapoB) is a strong predictor of cardiovascular disease (CVD), even in patients who achieve recommended LDL-Cholesterol (LDL-C) goals. ApoB level, an important correlate of metabolic syndrome (MetS), is influenced by several gene-environment interactions. Some of them are rare and can explain a large proportion of apoB variance, whereas others more common have variable effects. The aim of this study was to evaluate the association of interaction between smoking and common hyperapoB gene variants (PPARα-L162V, lipoprotein lipase loss-of function mutation, apo e4 allele or apo E2/2 genotype) with plasma apoB concentrations, according to the expression of MetS. Methods This study was performed among 1798 subjects. Smoking was defined as non/mild smokers vs. moderate-to-heavy smokers. ApoB levels were determined using nephelometry. Logistic regression models were used to document interactions between smoking habits and the presence of hyperapoB gene variants on the relative odds to exhibit increased plasma apoB concentrations. Results Around 29% of individuals with a low-risk lipid profile without MetS component had hyperapoB. Smoking and the presence of hyperapoB gene variants tended to be associated with higher plasma apoB levels even in presence of low-LDL-C. There was a significant interaction (P = 0.04) between the presence of ≥1 gene variants and smoking on the risk to exhibit hyperapoB among subjects with low risk profile in primary prevention. Conclusions Combination of life habits assessment and some common genes variants may detect a significant proportion of patients with increased apoB levels, and therefore a higher risk of CVD, who could have been initially perceived as low-risk.

Background Recent studies emphasize the importance of HDL function over HDL cholesterol measurement, as an important risk for cardiovascular diseases (CVD). We compared the HDL function of patients with acute coronary syndrome (ACS) and healthy controls. Methods We measured cholesterol efflux capacity of HDL using THP-1 macrophages labelled with fluorescently tagged (BODIPY) cholesterol. PON1 activities toward paraoxon and phenyl acetate were assessed by spectrophotometric methods. Results We recruited 150 ACS patients and 110 controls. The HDL function of all patients during acute phase and at six month follow-up was measured. The mean age of the patients and controls was 51.7 and 43.6 years respectively. The mean HDL cholesterol/apolipoprotein A-I levels (ratio) of patients during acute phase, follow-up and of controls were 40.2 mg/dl/ 112.5 mg/dl (ratio = 0.36), 38.3 mg/dl/ 127.2 mg/dl (ratio = 0.30) and 45.4 mg/dl/ 142.1 mg/dl (ratio = 0.32) respectively. The cholesterol efflux capacity (CEC) of HDL was positively correlated with apolipoprotein A-I levels during acute phase (r = 0.19, p = 0.019), follow-up (r = 0.26, p = 0.007) and of controls (r = 0.3, p = 0.0012) but not with HDL-C levels (acute phase: r = 0.07, p = 0.47; follow-up: r = 0.1, p = 0.2; control: r = 0.02, p = 0.82). Higher levels of cholesterol efflux capacity, PON1 activity and apolipoprotein A-I were associated with lower odds of development of ACS. We also observed that low CEC is associated with higher odds of having ACS if PON1 activity of HDL is also low and vice versa. Conclusion ACS is associated with reduced HDL functions which improves at follow-up. The predicted probability of ACS depends upon individual HDL functions and the interactions between them.

Background Genetic and environment factors affect the occurrence and development of coronary artery disease (CAD). Proprotein convertase subtilisin/kexin type 9 (PCSK9), has been investigated extensively in the field of lipid metabolism and CAD. We performed this case-control study to investigate the relationship between serum PCSK9 levels and PCSK9 polymorphisms and lipid levels and CAD risk in a southern Chinese population. Methods A hospital-based case-control study with 1, 096 subjects, including 626 CAD patients and 470 controls, were conducted. Genotyping of PCSK9 polymorphisms was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Results The frequencies of the AA, AG and GG genotypes of PCSK9 E670G polymorphism were 90.58, 9.27, and 0.16% in the CAD patients, compared with 88.72, 10.85 and 0.43% in the controls, respectively. No R46L variant was detected in this population. There were no significant differences in genotype and allele frequencies of PCSK9E670G polymorphism between the CAD group and the controls. Serum lipid levels were not significantly different in carriers with the G allele and those with the AA genotype. The median (QR) of PCSK9 concentration was 1205.00 ng/l (577.28–1694.13 ng/l) in cases and 565.87 ng/l (357.17–967.50 ng/l) in controls, respectively. Compared with controls, CAD patients had significantly higher PCSK9 levels (z = 4.559, P

Background Hypocholesterolemia is the most frequently encountered lipid abnormality in sickle cell disease (SCD). We enrolled pediatric patients to determine the relationships between lipid profile and parameters of hemolysis, oxidative stress and chronic inflammation in SCD. Methods The study involved 35 pediatric SCD patients and 19 healthy controls. Patients were crisis-free and had not received transfusions for the last 3 months. Total cholesterol, triglyceride, HDL-C, LDL-C, VLDL-C, apolipoprotein A1, apolipoprotein B, LCAT, LDH, bilirubin, haptoglobin, iron, ferritin, hemin, serum amyloid A (SAA), myeloperoxidase (MPO), uric acid, ALT and GGT levels were evaluated in patients’ blood. Results Patients had hypocholesterolemia depicted by lower levels of total cholesterol, HDL-C, LDL-C, as well as Apolipoprotein A1 and Apolipoprotein B compared to controls. The chronic hemolysis of SCD was evident in patients by higher LDH and bilirubin and almost undetectable haptoglobin levels. Hemin levels (as a measure of oxidized heme) were significantly increased in patients with SCD. Inflammation markers, SAA and MPO, were significantly increased in the patients as well. There were negative correlations between HDL-C and LDH, and Apo A1 and SAA. Hemin was positively correlated to MPO. Conclusion Hemolysis was associated with decreased HDL –C, and Inflammation was linked to decreased apolipoprotein A1 levels in our SCD patients. Therefore, we suggest that the HDL particle is altered during the course of the disease. The altered HDL in SCD may become dysfunctional and result with a slowing down of the reverse cholesterol transport.

Background Apolipoprotein CIII (apoCIII) is an independent risk for coronary heart disease (CHD). In this study, we investigated the associations among plasma apoCIII, hs-CRP and TNF-α levels and their roles in the clinical features of CHD in the Li and Han ethnic groups in China. Methods A cohort of 474 participants was recruited (238 atherosclerotic patients and 236 healthy controls) from the Li and Han ethnic groups. Blood samples were obtained to evaluate apoCIII, TNF-α, hs-CRP and lipid profiles. Chi-squared, t-tests, and Kruskal–Wallis or Wilcoxon–Mann–Whitney tests, Pearson or Spearman correlation tests and multiple unconditional logistic regression were employed to analyze lipid profiles and variations in plasma apoCIII, TNF-α, hs-CRP in subgroups of CHD and their contributions to CHD using SPSS version 20.0 software. Results Compared to healthy participants, unfavorable lipid profiles were identified in CHD patients with enhanced systolic pressure, diastolic pressure, fasting blood sugar (FBS), TG, TC, LDL-C, apoB, Lp(a) (P 0.05). Plasma apoCIII, TNF-α and hs-CRP contributed to the development of CHD (OR = 2.554, 7.252, 6.035, P

Background To investigate the association between the ratio of apolipoprotein B (apo B) / apolipoprotein A1 (apo A1) with all-cause mortality and cardiovascular events in peritoneal dialysis (PD) patients. Methods Eight hundred and sixty incident PD patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Outcomes were all-cause mortality and cardiovascular events. Associations between the apo B/apo A1 ratio with all-cause mortality and cardiovascular events were evaluated using multivariable-adjusted Cox models. Results Of the 860 patients, the mean age was 49.9 ± 14.5 years, 57.6% were men, and 19.3% were diabetic patients. The median apo B/apo A1 ratio was 0.65 (range: 0.22–2.24). During a median follow-up period of 27 months (interquartile range, 13 – 41 months), 202 deaths, and 145 cardiovascular events were recorded. After adjustment for age, sex, body mass index, diabetes, cardiovascular disease, systolic blood pressure, total Kt/V, estimated glomerular filtration rate, hemoglobin level, neutrophil to lymphocyte ratio and albumin, triglyceride, and cholesterol, as well as the use of lipid-lowering agents, the highest apo B/apo A1 ratio tertile was significantly associated with a hazard ratio for all-cause mortality of 1.60 (95% CI: 1.02 to 2.49, P = 0.040) and for cardiovascular events of 2.04 (95% CI: 1.21 to 3.44, P = 0.008). Conclusion An increased apo B/apo A1 ratio was independently associated with all-cause mortality and cardiovascular events in PD patients.

Background Elevated serum levels of apolipoprotein (apo) C1 may be an early protein marker of metabolic abnormality in women with polycystic ovary syndrome (PCOS). It is not clear, however, whether there are any relationships between the apoC1 rs4420638A/G and -317deletion (H1)/insertion (H2) polymorphisms and PCOS. We investigated the relationship between these two variants and the risk of PCOS, evaluated the genotypic effects on clinical, hormonal and metabolic indexes and plasma platelet-activating factor acetylhydrolase (PAF-AH) activity, and defined the association of apoC1 gene variants with apoE ε2/ε3/ε4 polymorphisms. Methods This is a cross-sectional study of 877 women with PCOS and 761 controls. The apoC1 rs4420638A/G genotype was determined by a Taqman real-time PCR allelic discrimination assay. The apoC1–317H1/H2 and apoE ε2/ε3/ε4 genotypes were measured using PCR and restriction fragment length polymorphism analysis. The clinical, hormonal and metabolic parameters and PAF-AH activity were measured. Results The frequencies of apoC1 rs4420638A/G and -317H1/H2 genotypes and alleles were similar between PCOS and control groups (P > 0.05). However, the rs4420638 G allele was related to increased serum luteinizing hormone, cholesterol and apoB levels, and the ratio of apoB to apoA1 (P

Background Abetalipoproteinemia and homozygous hypobetalipoproteinemia are classical Mendelian autosomal recessive and co-dominant conditions, respectively, which are phenotypically similar and are usually caused by bi-allelic mutations in MTTP and APOB genes, respectively. Instances of more complex patterns of genomic variants resulting in this distinct phenotype have not been reported. Methods A 43 year-old male had a longstanding severe deficiency of apolipoprotein (apo) B-containing lipoproteins and circulating fat soluble vitamins consistent with either abetalipoproteinemia or homozygous familial hypobetalipoproteinemia (FHBL). He also had acanthocytosis, a long term history of fat malabsorption, and mild retinopathy, but was free from coagulopathy, myopathy and neuropathy. He had taken high dose oral fat soluble vitamins since childhood. Results Targeted next generation DNA sequencing revealed several rare heterozygous missense variants in both MTTP and APOB genes known or predicted to be deleterious, in addition to a novel heterozygous missense variant in SAR1B, which encodes the gene causing chylomicron retention disease. Evaluation of first degree relatives with mild FHBL clarified the segregation of variants. Conclusions The proband’s characteristic phenotype likely resulted from an oligogenic interaction involving multiple rare variants in MTTP and APOB, and related genes, each of which individually was associated with a milder or minimal clinical and biochemical phenotype.