Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Lipids Health Dis. 2012 Jan 13;11:9. doi: 10.1186/1476-511X-11-9.
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.
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.
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.
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.
酰基辅酶 A：胆固醇酰基转移酶（ACAT）是细胞胆固醇稳态和动脉粥样硬化中的关键酶。已经表明，高脂血症小鼠的细胞胆固醇流出与血清高密度脂蛋白胆固醇（HDL-C）浓度相关受损。本研究旨在阐明 ACAT-1 rs1044925 单核苷酸多态性（SNP）与高脂血症患者血清脂质水平的关系。
本研究共纳入 821 名年龄在 15-80 岁之间的无亲缘关系的受试者（高脂血症组 476 名，正常血脂组 345 名）。采用聚合酶链反应和限制性片段长度多态性结合凝胶电泳对 ACAT-1 rs1044925 SNP 进行基因分型，然后通过直接测序进行确认。
正常血脂组和高脂血症组之间 ACAT-1 rs1044925 SNP 的基因型和等位基因频率无显著差异。在男性而非女性中，高脂血症组 AA 和 AC/CC 基因型之间的总胆固醇（TC）、HDL-C 和载脂蛋白（Apo）AI 水平存在差异（P < 0.05-0.01），C 等位基因携带者的血清 TC、HDL-C 和 ApoAI 水平高于非携带者。高脂血症患者中基因型与血清 HDL-C 和 ApoAI 水平的关联主要见于高胆固醇血症的男性患者，而不是高甘油三酯血症患者。在正常血脂组中，AA 和 AC/CC 基因型之间的血清脂质水平无显著差异。
本研究表明，男性高脂血症患者 ACAT-1 rs1044925 SNP 的 C 等位基因携带者的血清 TC、HDL-C 和 ApoAI 水平高于非携带者。ACAT-1 rs1044925 SNP 与血清 HDL-C 和 ApoAI 水平在高胆固醇血症患者中存在性别（男性）特异性关联。
