Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, P.R. China.
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi 830054, P.R. China.
Biosci Rep. 2019 Feb 26;39(2). doi: 10.1042/BSR20182129. Print 2019 Feb 28.
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.
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.
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 (=0.027, =0.012 and =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, =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 (<0.05).
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.
酰基辅酶 A:胆固醇酰基转移酶(ACAT)是唯一能够催化游离胆固醇与长链脂肪酸辅酶 A合成胆固醇酯(CE)的酶,在细胞胆固醇稳态中起着至关重要的作用。本研究旨在探讨中国新疆维吾尔族人群中 ACAT-2 基因的单核苷酸多态性(SNPs)是否与冠心病(CAD)相关。
我们设计了一项病例对照研究,纳入了 516 例 CAD 患者和 318 名年龄和性别匹配的对照者。采用改良多重连接依赖性探针扩增(iMLDR)法对所有研究对象的 ACAT-2 基因中的两个 SNPs(rs28765985 和 rs7308390)进行基因分型。
我们发现 rs28765985 的基因型、显性模型(CC+CT 与 TT)和超显性模型(CT 与 CC+TT)在 CAD 患者与对照组之间存在显著差异(=0.027,=0.012 和=0.035)。与 TT 基因型相比,rs28765985 的 C 等位基因与 CAD 风险显著升高相关[CC/CT 与 TT:比值比(OR)=1.48,95%置信区间(CI)=1.02-2.16,=0.04],校正混杂因素后结果仍具有统计学意义。rs28765985 的 CC/CT 基因型的 TC 和 LDL-C 水平显著高于 TT 基因型(<0.05)。
ACAT-2 基因的 rs28765985 与维吾尔族人群的 CAD 相关。携带 rs28765985 CC/CT 基因型或 C 等位基因的个体患 CAD 的风险增加。