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Objectives Our purpose was to determine whether the common polymorphisms (SNP-604, SNP1192, and SNP1719) in KDRare associated with risk of coronary heart disease. Background Vascular endothelial growth factor (VEGF) and its receptor KDR (kinase insert domain-containing receptor/fetal liver kinase-1, also called VEGFR2) play critical roles in angiogenesis and vascular repair, which are involved in the progress of coronary heart disease. Methods The association of the 3 polymorphisms with risk of coronary heart disease was determined in 2 independent case-control studies: one comprised of 665 patients with coronary heart disease and 1,015 control subjects, and the other comprised of 369 patients and 625 control subjects. The SNP functions of KDRgene were studied by using luciferase reporter assays, determination of serum levels of KDR, and ligand-binding assays. Results The 2 independent population studies showed that the 3 polymorphisms were associated with risk of coronary heart disease with odds ratios of 1.37 for SNP-604 (p = 0.006), 1.41 for SNP1192 (p = 0.011), and 1.37 for SNP1719 (p = 0.007) in the first population, and 1.40 for SNP-604 (p = 0.015), 1.75 for SNP1192 (p = 0.003), and 1.50 for SNP1719 (p = 0.010) in the second population. The SNP-604C–bearing KDRpromoter exhibited 68% of lower transcription activity than the SNP-604T–bearing promoter. The SNP1192 and SNP1719 could obviously influence the efficiency of VEGF binding to KDR. Conclusions The KDRpolymorphisms may serve as novel genetic markers for the risk of coronary heart disease.

Background and Purpose— It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study. Methods— We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and Hin fI digestion. Results— Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 μmol/L; P P P P =0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78). Conclusions— The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.

To observe the association between adiponectin and small dense low-density lipoprotein (sLDL-c) in coronary artery disease (CAD) patients. Furthermore, we sought to determine the association between single nucleotide polymorphisms (SNP) rs1501299 (+276G/T), rs266729 (-11365C/G) and the incidence of CAD.Consecutive subjects with chest discomfort were examined by coronary angiography and divided into non-CAD [n = 250, 147 male, mean age (60.26 ± 7.52) years] and CAD [n = 267, 153 male, mean age (60.79 ± 9.63) years] groups. Blood samples were collected from all participants following an overnight fasting for at least 12 hours. Plasma adiponectin levels were measured by competitive enzyme-linked immunosorbent assay (ELISA). The serum levels of sLDL-C and oxidized low-density lipoprotein (ox-LDL) were determined by ELISA. Genotypes in rs1501299 and rs266729 of the adiponectin were determined by polymerase chain reaction (PCR).1. The adiponectin levels were significantly lower [(306.17 ± 74.52) mg/L vs. (321.78 ± 86.28) mg/L], whereas sLDL-C and ox-LDL levels were significantly higher [(276.30 ± 45.55) ng/L vs. (249.00 ± 32.02) ng/L and (545.06 ± 115.46) µg/L vs. (497.74 ± 106.09) µg/L, P0.05] in CAD group than non-CAD group. 2. Adiponectin level was negatively associated with sLDL-C, whereas sLDL-C positively correlated with ox-LDL in all subjects. 3. Genotype distribution and allele frequencies of rs1501299 and rs266729 were similar between CAD and non-CAD subjects and not related to the serum levels of adiponectin, sLDL-C and ox-LDL.Reduced adiponectin and increased sLDL-C were independent risk factors for coronary artery disease. Genetic polymorphisms in rs1501299 and rs266729 were not linked with coronary artery disease.

The purpose of the present study was to identify the relationship between the plasma level of adiponectin and in-stent restenosis of patients with coronary heart disease after coronary stenting.The study population comprised 119 individuals (92 men) who underwent stent implantation, including 65 subjects without in-stent restenosis (group A) and 54 patients with in-stent restenosis (group B). The level of plasma adiponectin was measured using ELISA. Coronary angiography was performed immediately before and after implanting stent and 9 - 12 months later.Baseline characteristics including drug use after PCI were similar between the groups. The rate of implanting bare metal stent is 8 (12.31%) and 6 (11.11%), TAXUS drug-eluting stent is 11 (16.92%) and 10 (18.52%) and CYPHER drug-eluting stent is 46 (70.77%) and 38 (70.37%) respectively (all P0.05). Plasma level of adiponectin in patient of group A was significantly higher than that in group B [(15.16 +/- 5.02) mg/L vs. (10.01 +/- 4.93) mg/L, P0.05]. The quantitative coronary angiography (QCA) showed that lesion length was similar between groups [(15.82 +/- 6.67) mm vs. (13.40 +/- 4.20) mm, P0.05], minimum lumen diameter (MLD) and stenosis rate were also similar before and after implanting stent (P0.05) and acute gain was (1.48 +/- 0.65) mm vs. (1.19 +/- 0.37) mm (P0.05). MLD was higher in group A than that in group B [(2.55 +/- 0.53) mm vs. (0.57 +/- 0.60) mm, P0.01] at 9 - 12 months follow up. Restenosis rate [(24.2 +/- 11.2)% vs.(81.0 +/- 19.1)%, P0.01] and late lumen loss [(0.50 +/- 0.34) mm vs. (1.60 +/- 0.54) mm, P0.01] were lower in group A than in group B.The lower plasma adiponectin level might be associated with in-stent restenosis after coronary stenting.

To investigate the relationship between paraoxonase (PON) polymorphisms and serum homocysteine thiolactone (HTL) and coronary heart diseases.In this prospective study, serum complex of HTL levels using ELISA, and the lever of serum Hcy using high pressure liquid chromatography (HPLC), determined the PON1/T(-107)C and PON2/C311S genotypes using PCR-restriction fragment length polymorphisms 203 were measured in patients with angiographic documented coronary heart disease (CAD) and 117 controls.Serum levels of Hcy and the complex of HTL in CAD patients were significantly higher than that in controls (P0.05). No significant difference was found in frequencies of PON1/T(-107)C genotypes and alleles (P0.05) between CAD patient and controls. The PON2/C311S (SS) genotype was lower in CAD patients than that in controls (P0.05), while the frequency of allele was similar between the two groups (P0.05). The T allele of PON1/T(-107)C and S alleles of PON2/C311S polymorphism were associated with lower plasma Hcy and HTL complex [Hcy (11.83 +/- 4.76) micromol/L vs (15.32 +/- 10.32) micromol/L, P0.05; HTL complex (24.36 +/- 9.30) U/ml vs (32.05 +/- 10.44) U/ml, P0.05]. The genetype PON2 and allele C were higher in CAD patients with type 2 diabetes than that in CAD patients without type 2 diabetes and controls (P0.005).The elevation of serum Hcy and the complex of HTL were associated with increased risk of coronary heart disease. The allele PON1/(-107)T and PON2/311S might be protective for the development of atherosclerosis.

To assess the association of the metabolic syndrome with stroke in Chinese using the definition of ATP III, and revised definition according to Chinese criteria for abdominal obesity.Multi-center case control study, 1934 first-ever-stroke patients (Atherothrombosis, lacunar infarction, and intracerebral hemorrhage) aged 30 to 74 years were sequentially recruited. And 1839 age, gender and geographically matched subjects were included as controls.The prevalence of metabolic syndrome defined by either ATP III or Chinese criteria was significantly increasing in patients with lacunar infarction, cerebral atherosclerosis, or intracerebral hemorrhage than control subjects. After age- and sex-adjusted and further adjusted age, sex, total cholesterol, smoking, drinking, and education levels, the metabolic syndrome defined by ATP III criteria was associated with a 2.7 to 4.3 fold and 2.5 to 4.0 fold higher risk of the three stroke subtypes, respectively.the metabolic syndrome defined by ATP III and revised according to Chinese criteria of abdominal obesity was positively associated with the risk of stroke in our case control study. This study underscores the need for well-designed prospective study in Chinese to give further evidence to the link between metabolic syndrome and stroke.

To explore the association between alpha-adducin (ADD1) G/W460 and intracerebral hemorrhage (ICH) in Chinese.Samples of peripheral blood were collected from 456 patients with ICH diagnosed by CT or MRI from 7 clinical centers in China and 454 age, sex, and geographically matched subjects as controls. The ADD1 G/W460 polymorphism was detected by PCR. Information about prior exposure to various potential risk factors was collected by questionnaire survey.The distribution of ADD1gene G460W polymorphisms in the ICH patients and controls were in agreement with the Hardy-Weinberg proportion. The prevalence of 460W allele among ICH cases was 82.2%, higher than that in the controls (76.0%, crude odds ratio, 1.46; 95% CI, 1.05 to 2.05). The ADD1 460W allele was still significantly associated with ICH after adjustment for hypertension and other ICH putative risk factors (adjusted odds ratio, 1.38; 95% CI, 1.01 to 1.88).Alpha-adducin gene G/W 460 polymorphism is significantly associated with the risk of ICH. This association does not appear to be mediated by established ICH risk factors, specifically hypertension status.

To investigate the relationship between small, dense LDL (sLDL) and stroke in Chinese population.The plasma level of sLDL was examined by 2% - 16% nondenatured gradient gel electrophoresis in 204 patients with stroke, including 103 cases of ischemic cerebral infarction (ICI), 51 cases of lacunar infarction (LI), and 50 cases of subcortical hemorrhage (SH), and in 341 sex- and age-matched controls in China. Traditional risk factors for stroke were investigated as well.The plasma level of sLDL was significantly higher in patients with ICI and LI (54 +/- 8% and 52 +/- 7%) than in the controls (47 +/- 11%, both P0.01). However, the plasma sLDL of the CH patients was 50 +/- 9%, not significantly different from that of the controls (P0.05). Multiple stepwise regression analysis showed that sLDL was significantly associated with systolic blood pressure, age, and the levels of triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (all P0.05). Multivariate logistic regression analysis showed that those with sLDL50% had increase of risk of ischemic cerebral infarction (OR = 3.1, 95% CI 1.649 - 5.691, P0.001) independent of other risk factors. The relationship between sLDL abnormality and LI and between sLDL abnormality and SH had no statistical significance (both P0.05).sLDL is significantly associated with ischemic cerebral infarction independent of other risk factors in Chinese population. sLDL may be a new marker for stroke at least in this Chinese population.