The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population.
ABSTRACT: Hypercholesterolemia arising from abnormal lipid metabolism is one of the critical risk factors for coronary artery disease (CAD), however the roles of genetic variants in lipid metabolism-related genes on premature CAD (? 60 years old) development still require further investigation. We herein genotyped four single nucleotide polymorphisms (SNPs) in lipid metabolism-related genes (rs1132899 and rs5167 in APOC4, rs1801693 and rs7765781 in LPA), aimed to shed light on the influence of these SNPs on individual susceptibility to early-onset CAD.Genotyping of the four SNPs (rs1132899, rs5167, rs1801693 and rs7765781) was performed in 224 premature CAD cases and 297 control subjects (? 60 years old) using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. The association of these SNPs with premature CAD was performed with SPSS software.Multivariate logistic regression analysis showed that C allele (OR = 1.50, P = 0.027) and CC genotype (OR = 2.84, P = 0.022) of APOC4 rs1132899 were associated with increased premature CAD risk, while the other three SNPs had no significant effect. Further stratified analysis uncovered a more evident association with the risk of premature CAD among male subjects (C allele, OR = 1.65, and CC genotype, OR = 3.33).Our data provides the first evidence that APOC4 rs1132899 polymorphism was associated with an increased risk of premature CAD in Chinese subjects, and the association was more significant among male subjects.
Project description:Single nucleotide polymorphisms (SNPs) of the USF1 gene (upstream stimulatory factor 1) influence plasma lipid levels. This study aims to determine whether USF1 SNPs interact with traditional risk factors of atherosclerosis to increase coronary artery disease (CAD) risk. In the present study serum lipid levels and USF1 gene polymorphisms (rs2516839 and rs3737787) were determined in 470 subjects: 235 patients with premature CAD and 235 controls. A trend of increasing triglycerides (TG) levels in relation to the C allele dose of rs2516839 SNP was observed. The synergistic effect of cigarette smoking and C allele carrier state on CAD risk was also found (SIM = 2.69, p = 0.015). TG levels differentiated significantly particular genotypes in smokers (1.53 mmol/L for TT, 1.80 mmol/L for CT and 2.27 mmol/L for CC subjects). In contrast, these differences were not observed in the non-smokers subgroup (1.57 mmol/L for TT, 1.46 mmol/L for CT and 1.49 mmol/L for CC subjects). In conclusion, the rs2516839 polymorphism may modulate serum triglyceride levels in response to cigarette smoking. Carriers of the C allele seem to be particularly at risk of CAD, when exposed to cigarette smoking.
Project description:INTRODUCTION:Asian Indians have a propensity for premature, severe, and diffuse coronary artery disease (CAD). Several single-nucleotide polymorphisms (SNPs) in the 'core CAD' region of the chromosomal region 9p21.3 are known to be strongly associated with CAD. OBJECTIVES:We aimed to study SNPs in the 9p21.3 region associated with CAD and premature CAD and identify their association with demographic and clinical characteristics in an Asian Indian population. METHODS:SNP genotyping was performed for 30 SNPs of the 9p21.3 region using MassARRAY® technology. Along with demographic and SNP data analysis, we also performed multivariate logistic regression analysis and multifactor dimensionality reduction analysis to study SNP-SNP and SNP-demographic/clinical variable interactions. RESULTS:Our results suggest that females are at a higher risk of premature CAD. We found that SNPs rs1333045 (CC), rs16905599 (AA), rs2383206 (GG), rs2383208 (AG), and rs4977574 (GG) were significantly associated with premature CAD. When adjusted for covariates/confounders, we found that rs2383206 showed the strongest risk association with CAD followed by rs16905599 and rs2383208. Further, SNPs rs1333049 (CC) and rs4977574 (GG) were found to be exclusively associated with premature CAD cases, suggesting their potential as genetic markers for premature CAD in the local population. Upon gender-based stratification, it was found that rs10757272 (TT and TC) is significantly associated with eightfold to ninefold CAD risk specifically among females. SNP rs7865618 (GG) is significantly associated with more than 2.5-fold CAD risk specifically among males. CONCLUSION:Our study suggests that SNPs at the 9p21 risk locus may be used to generate a reliable genetic risk score along with markers at other loci.
Project description:Background:This study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population. Methods:Genotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 SNPs in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. Another group of 724 hyperlipidemic patients was selected and treated with atorvastatin calcium tablet 20 mg/day for 8 weeks. Results:The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR = 0.68, 95% CI = 0.47-0.99, P = 0.043 for CT/TT vs. CC) and IS (adjusted OR = 0.55, 95% CI = 0.38-0.80, P = 0.020 for CT/TT vs. CC). There was no significant association between the four SNPs and angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype (P < 0.001; a P < 0.0018 was regarded statistically significant by the Bonferroni correction). The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment (P < 0.001). Conclusions:The observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Chinese Han population, especially the ANGPTL4 rs4076317 and rs2967605 SNPs.
Project description:BACKGROUND: Four single nucleotide polymorphisms (SNPs) (rs2237892, rs2237895, rs2237897, and rs2283228) in KCNQ1 are reported to be associated with type 2 diabetes mellitus (T2DM), possibly caused by a reduction in insulin secretion and higher fasting glucose, but the results are inconsistent. We investigated whether these 4 genetic markers are associated with serum lipid metabolism in a middle-aged Chinese Han population. METHODS: We enrolled 398 consecutive patients, including 180 with premature coronary artery disease (CAD) (male < 55 years, female < 65 years) and 218 controls without documented CAD. All subjects were genotyped for 4 SNPs by using the ligase detection reaction method. Fasting blood sugar (FBS) and plasma concentrations of total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1(apo A1), and apolipoprotein B (apo B) were determined by standard biochemical methods. Main anthropometric and metabolic characteristics are analyzed among 3 genotypes at rs2283228, rs2237895, rs2237897, or rs2237892 in KCNQ1. RESULTS: The 3 genotypes AA, AC, and CC were present in rs2283228 and rs2237895, and the 3 genotypes CC, CT, and TT were present in rs2237897 and rs2237892. The minor genotypes CC at rs2283228 and TT at rs2237892 were associated with higher levels of TG (P = 0.007 and 0.026, respectively). Furthermore, subjects with the CC genotype at rs2283228 had lower levels of HDL-C and apo A1 than in the other 2 genotype groups (P = 0.052 and 0.055, respectively). No other associations were detected between these 4 SNPs and FBS or other lipid parameters. CONCLUSIONS: Our data suggest that rs2283228 and rs2237892 in KCNQ1 are associated with lipid metabolism in a middle-aged Chinese Han population.
Project description:Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190-4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012-2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233-4.348, P = 0.015).Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.
Project description:7-Alpha cholesterol hydroxylase (CYP7A1), the first enzyme of classic conversion pathway leading from cholesterol to bile acids synthesis, is encoded by CYP7A1 gene. Its single nucleotide polymorphisms (SNPs) influence serum lipid levels and may be related to impaired lipid profile leading to coronary artery disease (CAD). The aim of the present study was to analyze the possible association between the rs7833904 CYP7A1 polymorphism and premature CAD.Serum lipid levels and rs7833904 SNP were determined in 419 subjects: 200 patients with premature CAD and 219 age and sex matched controls.The A allele carrier state was associated with CAD (OR = 1.76, 95% CI; 1.14-2.71, P = 0.014). The effect was even stronger in the male subgroups (OR = 2.16, 95% CI; 1.28-3.65, P = 0.003). There was no effect in the females. Risk factors of CAD and clinical phenotype of atherosclerosis were not associated with genotype variants of the rs7833904 SNP. Lipid profiles also did not differ significantly between individual genotypes.The CYP7A1 rs7833904 polymorphism may modify the risk of CAD. This effect is especially strong in male subjects. The studied polymorphism does not significantly influence serum lipid levels, in the present study.
Project description:BACKGROUND:Hyperlipidemia is a major risk factor for coronary artery disease (CAD). As F-box and WD repeat domain-containing 7 (FBXW7) gene is an important regulating factor for lipid metabolism, the aim of the present study is to assess the association between human FBXW7 gene polymorphisms and CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China. METHODS:A total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three single nucleotide polymorphisms (SNPs) rs2255137 T>C, rs2292743 A>T, rs35311955 G>C of FBXW7 were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method. RESULTS:We found that the rs2255137 CC genotype was very common in the CAD patients compared with the control subjects in the Uygur Chinese populations. After adjustments for several confounders: age, gender, smoking, drinking, hypertension, diabetes, TG, TC, HDL-C and LDL-C, this association remained significant. Furthermore, we investigated the relationships between rs2255137 genotypes and the circulating serum lipid levels and found that people carrying the C allele of rs2255137 may have higher serum lipid levels in the Uygur Chinese populations. CONCLUSION:Our results indicate that rs2255137 in FBXW7 gene is associated with CAD in the Uygur Chinese population in China.
Project description:BACKGROUND: Abnormal lipids is one of the critical risk factors for myocardial infarction (MI), however the role of genetic variants in lipid metabolism-related genes on MI pathogenesis still requires further investigation. We herein genotyped three SNPs (LRP6 rs2302685, LDLRAP1 rs6687605, SOAT1 rs13306731) in lipid metabolism-related genes, aimed to shed light on the influence of these SNPs on individual susceptibility to MI. METHODS: Genotyping of the three SNPs (rs2302685, rs6687605 and rs13306731) was performed in 285 MI cases and 650 control subjects using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. The association of these SNPs with MI and lipid profiles was performed with SPSS software. RESULTS: Multivariate logistic regression analysis showed that C allele (OR?=?1.62, P?=?0.039) and the combined CT/CC genotype (OR?=?1.67, P?=?0.035) of LRP6 rs2302685 were associated with increased MI risk, while the other two SNPs had no significant effect. Further stratified analysis uncovered a more evident association with MI risk among younger subjects (?60 years old). Fascinatingly, CT/CC genotype of rs2302685 conferred increased LDL-C levels compared to TT genotype (3.0 mmol/L vs 2.72 mmol/L) in younger subjects. CONCLUSIONS: Our data provides the first evidence that LRP6 rs2302685 polymorphism is associated with an increased risk of MI in Chinese subjects, and the association is more evident among younger individuals, which probably due to the elevated LDL-C levels.
Project description:Introduction:First-degree relatives of individuals with premature coronary artery disease (CAD) are at increased risk of CAD. The research hypothesis of this project assumes that there are differences in the metabolic profiles between individuals with and without a positive family history (FH) of premature CAD. Material and methods:The study group will comprise healthy patients (n = 500) aged 18-35 years with a FH of premature CAD, and the control group (n = 500) will consist of healthy subjects without a FH of premature CAD. Blood tests assessing the lipid profile will be carried out. Patients will respond to a questionnaire regarding FH and dietary habits. Measurement of carotid intima media thickness will be performed. Analysis of single-nucleotide polymorphisms (SNPs) associated with premature CAD will be carried out for every patient. Metabolomic profiling will be performed using a high-sensitivity Bruker AVANCE II 600 MHz NMR spectroscope. Results:The results of this study will include a comparison of metabolic profiles assessed by 1H-NMR spectroscopy in the study and control groups and the results of analyses of the relationship between the metabolic profiles and genetic risk score calculated based on evaluated SNPs associated with premature CAD. Conclusions:This study will deepen our knowledge of the aetiopathogenesis of atherosclerosis by identifying metabolic patterns associated with a positive FH of premature CAD. Obtaining a detailed FH will enable adjustments for major risk factors of premature CAD in the proband's first-degree relatives. This research project also provides a chance to discover new biomarkers associated with the risk of premature CAD.
Project description:The present study was to determine the association of two single nucleotide polymorphisms (SNPs) in the glucokinase regulator gene (GCKR) and serum lipid levels, and the risk of coronary artery disease (CAD) and ischemic stroke (IS). Genotypes of the GCKR rs1260326 and rs8179206 in 1736 unrelated subjects (CAD, 584; IS, 555; and healthy controls; 597) were determined by the Snapshot technology platform. The genotypic and allelic frequencies of rs1260326 and rs8179206 were not different among the three groups (P > 0.05). The subjects with rs1260326TT genotype had higher serum low-density lipoprotein cholesterol (LDL-C) levels in controls, and higher triglyceride (TG) levels in CAD patients than the subjects with CC and CT genotypes after adjustment for age, sex, body mass index, blood pressure, alcohol consumption, and cigarette smoking (P < 0.05). The rs1260326TT genotype was also associated with decreased risk of IS in females (OR = 0.37, 95% CI: 0.18-0.76, P = 0.007). The present study shows that the GCKR rs1260326TT genotype is associated with high LDL-C in controls, high TG levels in CAD patients, and a decreased risk of IS in females.