The influence of the acyl-CoA:cholesterol acyltransferase-1 gene (-77G→A) polymorphisms on plasma lipid and apolipoprotein levels in normolipidemic and hyperlipidemic subjects
The influence of the acyl-CoA:cholesterol acyltransferase-1 gene (-77G→A) polymorphisms on plasma lipid and apolipoprotein levels in normolipidemic and hyperlipidemic subjects
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DOI：
10.1016/s1388-1981(04)00025-3
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发表时间：
2004-06-01
影响因子：
4.8
通讯作者：
Fukuyama, S
中科院分区：
文献类型：
--
作者：
Ohta, T;Takata, K;Fukuyama, S
背景：酰基辅酶A：胆固醇酰基转移酶（ACAT）在细胞胆固醇稳态中起重要作用。已报告了ACAT的两种亚型（ACAT-1和ACAT-2）。ACAT抑制剂不仅可以预防动脉粥样硬化的形成，而且还可以诱导其在动物中消退。在人类中，ACAT抑制剂显示具有降脂作用。本研究旨在探讨ACAT-1基因变异与高脂血症的关系。方法和结果：为了鉴定遗传变异，我们通过直接测序筛选了30名高脂血症受试者。结果，鉴定了错义变体（R526 G）和5'非翻译区中的变体（-77G--> A）。在178名无关的正常血脂和441名无关的高血脂受试者中测定每个变异体的基因型频率。正常血脂组和高血脂组R526 G变异的等位基因频率分别为0.676和0.633。正常血脂组和高血脂组-77G->A等位基因频率分别为0.503和0.515。在两种变异体中，血脂正常和高血脂受试者之间的等位基因频率差异不显著。R526 G变体不影响研究对象的血脂或载脂蛋白的血浆浓度。而在高脂血症患者中，-77G-> A变异者的血浆HDL-C和apoA-I浓度显著高于无变异者。结论：高脂血症患者存在ACAT-1基因的两种变异。- 77 G--> A变体仅在高脂血症受试者中影响血浆HDL浓度。这些数据表明，细胞内FC浓度可能会调节血浆HDL浓度。(C)2004 Elsevier B. V.保留所有权利。
Background: Acyl-CoA: cholesterol acyltransferase (ACAT) plays important roles in cellular cholesterol homeostasis. Two isoforms of ACAT have been reported (ACAT-1 and ACAT-2). ACAT inhibitors cannot only prevent atherosclerosis formation, but may also induce its regression in animals. In humans, an ACAT inhibitor was shown to have a lipid-lowering effect. The present study was carried out to clarify the relationship between ACAT-1 gene variants and hyperlipidemia. Methods and results: To identify genetic variants, we screened 30 subjects with hyperlipidemia by direct sequencing. As a result, a missense variant (R526G) and a variant in the 5' untranslated region (- 77G --> A) were identified. The genotype frequencies of each variant were determined in 178 unrelated normolipidemic and 441 unrelated hyperlipidemic subjects. The alleles frequencies of the R526G variant in normolipidemic and hyperlipidemic subjects were 0.676 and 0.633, respectively. The alleles frequencies of the - 77G -->A variant in normolipidemic and hyperlipidemic subjects were 0.503 and 0.515, respectively. Differences in allele frequencies between normolipidemic and hyperlipidemic subjects were not significant in both variants. R526G variant did not affect plasma concentrations of lipids or apolipoproteins in subjects studied. However, among hyperlipidemic subjects, plasma concentrations of HDL-C and apoA-I in subjects with - 77G --> A variant were significantly higher than those in subjects without variant. Conclusion: Two variants in ACAT-1 gene were identified in subjects with hyperlipidemia. - 77G --> A variant affects plasma HDL concentrations only in hyperlipidemic subjects. These data suggest that the intracellular FC concentration might modulate plasma HDL concentrations. (C) 2004 Elsevier B.V. All rights reserved.