Acyl-CoA: cholesterol acyltransferases-2 gene polymorphism is associated with increased susceptibility to coronary artery disease in Uygur population in Xinjiang, China.
ABSTRACT: BACKGROUND:Acyl-CoA: cholesterol acyltransferases (ACAT) is the only enzyme that catalyzes the synthesis of cholesterol esters (CE) from free cholesterol and long-chain fatty acyl-CoA and plays a critical role in cellular cholesterol homeostasis. In the present study, our primary objective was to explore whether the single-nucleotide polymorphisms (SNPs) in ACAT-2 gene were associated with coronary artery disease (CAD) in Uygur subjects, in Xinjiang, China. METHODS:We designed a case-control study including 516 CAD patients and 318 age- and sex-matched control subjects. Using the improved multiplex ligation detection reaction (iMLDR) method, we genotyped two SNPs (rs28765985 and rs7308390) of ACAT-2 gene in all subjects. RESULTS:We found that the genotypes, the dominant model (CC + CT vs TT) and over-dominant model (CT vs CC + TT) of rs28765985 were significantly different between CAD patients and the controls (P=0.027, P=0.012 and P=0.035, respectively). The rs28765985 C allele was associated with a significantly elevated CAD risk [CC/CT vs TT: odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.02-2.16, P=0.04] after adjustment for confounders. The TC and LDL-C levels were significantly higher in rs28765985 CC/CT genotypes than that in TT genotypes (P<0.05). CONCLUSIONS:Rs28765985 of ACAT-2 gene are associated with CAD in Uygur subjects. Subjects with CC/CT genotype or C allele of rs28765985 were associated with an increased risk of CAD.
Project description:The present study was performed to clarify the association between the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) single nucleotide polymorphism (SNP) rs1044925 and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Polymerase chain reaction and restriction fragment length polymorphism was performed to determine the genotypes of the ACAT-1 SNP rs1044925 in 1730 unrelated subjects (CAD, 587; IS, 555; and healthy controls; 588). The genotypic and allelic frequencies of rs1044925 were significantly different between the CAD patients and controls (p = 0.015) and borderline different between the IS patients and controls (p = 0.05). The AC/CC genotypes and C allele were associated with a decreased risk of CAD and IS (CAD: p = 0.014 for AC/CC vs. AA, p = 0.022 for C vs. A; IS: p = 0.014 for AC/CC vs. AA; p = 0.017 for C vs. A). The AC/CC genotypes in the healthy controls, but not in CAD or IS patients, were associated with an increased serum high-density lipoprotein cholesterol (HDL-C) concentration. The present study shows that the C allele carriers of ACAT-1 rs1044925 were associated with an increased serum HDL-C level in the healthy controls and decreased risk in CAD and IS patients.
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:Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) -250G > A, endothelial lipase gene (LIPG) 584C > T, methylenetetrahydrofolate reductase (MTHFR) 677C > T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T > C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT-1 AC, LIPC GA and AA, and SCARB1 TT; LDL-R A-A- and LIPC GA; and SCARB1 TT were interacted with overweight/obesity to increase systolic, diastolic blood pressure (SBP, DBP) and pulse pressure (PP) levels; respectively. The genotypes of ACAT-1 CC; ACAT-1 AA and CC were interacted with overweight/obesity to decrease SBP, PP levels (p < 0.01-0.001); respectively. The differences in blood pressure levels between normal weight and overweight/obese subjects might partly result from different interactions of several SNPs and overweight/obesity.
Project description:BACKGROUND: Our previous studies have showed that the rs5888 single nucleotide polymorphism (SNP) in Scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in the general Chinese populations. The present study was undertaken to detect the associations between rs5888 SNP and the risk of coronary artery disease (CAD) and ischemic stroke (IS). METHODS: A total of 1,716 unrelated subjects (CAD, 601; IS, 533; and healthy controls, 582) were included in this study. Genotyping of the rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotypic frequencies of SCARB1 rs5888 SNP were different between CAD patients and controls, the subjects with TT genotype had high risk of CAD (OR = 1.76, P = 0.038 for TT vs. CC; and OR = 1.75, P = 0.036 for TT vs. CC/CT). There was no significant association between genotypes and the risk of IS. Further analysis showed that the subjects with TT genotype in the total population had lower levels of high-density lipoprotein cholesterol than the subjects with CC/CT genotypes (P < 0.05), the subjects with TT genotype in controls but not in CAD or IS patients had higher levels of serum LDL-C and ApoB than those with CC genotype (P < 0.05 for each). CONCLUSIONS: The present study suggests that the SCARB1 rs5888 SNP influences serum lipid levels, and is associated with the risk of CAD.
Project description:BACKGROUND: Acyl-CoA:cholesterol acyltransferase (ACAT) is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP) and serum lipid levels in the hyperlipidemic subjects. METHODS: A total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345) aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: There was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC), HDL-C and apolipoprotein (Apo) AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (P < 0.05-0.01), the C allele carriers had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. The association of genotypes and serum HDL-C and ApoAI levels in hyperlipidemia was found mainly in the male subjects with hypercholesterolemia but not in those with hypertriglyceridemia. There were no significant differences in serum lipid levels between the AA and AC/CC genotypes in the normolipidemic subjects. CONCLUSIONS: The present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male)-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.
Project description:Several studies suggest an important role of Acyl-CoA: cholesterol acyltransferase-1(ACAT-1) in the development of atherosclerosis. The aim of present study was to investigate whether there exists a possible correlation between genetic variations in ACAT-1 genes and coronary artery disease (CAD) risk. Four polymorphisms (rs1044925, rs11545566, rs12121758 and rs10913733) were finally selected and genotyped in 750 CAD patients and 580 health controls, using the improved multiplex ligation detection reaction (iMLDR) method. We found that the rs11545566 G allele was associated with a significantly elevated CAD risk [GG vs. AA: adjusted odds ratio (AOR) = 1.62, 95% confidence interval (CI) = 1.13-2.32, P = 0.008; GA/GG vs. AA: AOR = 1.67, 95% CI = 1.22-2.29, P = 0.001]. The rs10913733 G allele was also associated with a significantly elevated CAD risk (GG vs. TT: AOR = 1.57, 95% CI = 1.08-2.28, P = 0.018; GT/GG vs. TT: AOR = 1.39, 95% CI = 1.07-1.79, P = 0.013). Multivariate linear regression analysis showed that the rs11545566 polymorphism was independently associated with the Gensini scores (P = 0.005). The Gensini score of subjects in the variant GG genotype group and the GG/GA genotype group were higher than the score of subjects in the AA genotype group (32.49 ± 26.60 and 31.26 ± 26.96 vs. 23.45 ± 21.64; P = 0.001 and 0.002, respectively). Our results demonstrate that ACAT-1 rs1154556 and rs10913733 polymorphism are novel genetic factors in the development of CAD. Rs11545566 was also associated with the severity of CAD.
Project description:Hyperlipidemia is a major risk factor for coronary artery disease (CAD). The current study was designed to explore the possible correlation between single nucleotide polymorphisms (SNPs) in the lipid homeostasis regulatory genes F-box and WD repeat domain-containing 7 (FBXW7) and sterol regulatory element-binding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China.In the Uygur Chinese population, rs9902941 in SREBP-1 and rs10033601 in FBXW7 were found to be associated with CAD in a recessive model (TT vs. CT + CC, P = 0.032; GG vs. AG + AA, P = 0.010, respectively), and rs7288536 in SREBP-2 was found to be associated with CAD in an additive model (CT vs. CC + TT, P = 0.045). The difference was statistically significant in the Uygur Chinese population after multivariate adjustments [Odds ratio (OR) = 1.803, 95% confidence interval (CI): 1.036~3.137, P = 0.037; OR = 1.628, 95% CI: 1.080~2.454, P = 0.020; OR = 1.368; and 95% CI: 1.018~1.837, P = 0.037, respectively]. There were also significant interactions between the above-mentioned models in the Uygur Chinese population. However, these relationships were not observed before or after multivariate adjustment in the Han Chinese population.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 SNPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method.The results of this study indicate that variations in the lipid regulatory pathway genes FBXW7 and SREBPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) are associated with CAD in the Uygur Chinese population in Xinjiang, China.
Project description:Previous genome-wide association studies have shown that the rs10248618 single nucleotide polymorphism (SNP) in the dynein axonemal heavy chain 11 gene (DNAH11) has been associated with serum high-density lipoprotein cholesterol (HDL-C) levels. However, little is known about such association in the Chinese population. The present study was performed to clarify the association between the DNAH11 rs10248618 SNP and serum lipid traits and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Genotypes of the DNAH11 rs10248618 SNP in 1,213 unrelated patients (CAD, 600 and IS, 613) and 631 healthy controls were determined by snapshot technology. The genotypic and allelic frequencies of the SNP were significantly different between the CAD/IS patients and the controls (P < 0.01 for all). The CT/TT genotypes and the T allele were associated with an increased risk of CAD and IS (CAD: P < 0.01 for CT/TT vs. CC and T vs. C; IS: P < 0.01 for CT/TT vs. CC and T vs. C). The CT/TT genotypes in the healthy controls, but not in CAD or IS patients, were associated with a decreased serum HDL-C and apolipoprotein (Apo) A1 concentration. These results suggest that the DNAH11 rs10248618 SNP is associated with the risk of CAD and IS in our study population. It is likely to increase the risk of CAD and IS by reducing serum HDL-C and ApoA1 levels.
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:Numerous studies have shown a relationship between cholesteryl ester transfer protein (CETP) polymorphism in the synthesis of high-density lipoprotein cholesterol (HDL-C) and the coronary artery disease (CAD) susceptibility, but the results have remained inconsistent. In addition, there was no study exploring the relationship between CETP polymorphisms and atherogenic index of plasma (AIP) levels.We conducted a case-control study to evaluate the relationship between CETP rs708272 polymorphism and CAD risk and lipid levels in Chinese Han population. 556 CAD patients and 414 controls undergoing coronary angiography were consecutively enrolled in the hospital-based study. Polymerase chain reaction-ligase detection reaction (PCR-LDR) method was used to detect the different genotypes at rs708272.No significant association between CETP rs708272 polymorphism and CAD risk was observed in different genetic models. In the whole population, participants with TT genotype had higher HDL-C levels (1.17?±?0.31?mmol/L vs 1.09?±?0.29?mmol/L, P?=?.001) and lower AIP levels (0.08?±?0.35 vs 0.16?±?0.31, P?=?.004) compared to those with CC genotype, after adjusting for age, gender, smoking, essential hypertension (EH), and DM. The T allele carriers had higher HDL-C levels than the T allele non-carriers (1.13?±?0.29?mmol/L vs 1.09?±?0.29?mmol/L, P?=?.023). Furthermore, subgroup analyses based on gender were carried out. In males, the results showed that participants with TT genotype had significant higher HDL-C levels and lower AIP levels compared with CC genotype (P?<.05). In addition, males with CT+TT genotypes had higher HDL-C levels and lower AIP levels than those with CC genotypes (HDL-C: CT+TT 1.11?±?0.31vs CC 1.06?±?0.30?mmol/L, P?=?.041; AIP: CT+TT 0.12?±?0.32vs CC 0.16?±?0.31, P?=?.034, respectively). However, there were no significant associations between lipid levels and CETP rs708272 polymorphism in females, after adjusting for confounders.CETP rs708272 polymorphism has a gender-specific effect on lipid and AIP levels but not on the risk of CAD.