Insertion/deletion polymorphism in clusterin gene influences serum lipid levels and carotid intima-media thickness in hypertensive Japanese females
Insertion/deletion polymorphism in clusterin gene influences serum lipid levels and carotid intima-media thickness in hypertensive Japanese females
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DOI：
10.1016/j.bbrc.2005.04.069
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发表时间：
2005-06-17
影响因子：
3.1
通讯作者：
Kawano, Y
中科院分区：
文献类型：
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作者：
Miwa, Y;Takiuchi, S;Kawano, Y
簇蛋白与脂质代谢和动脉粥样硬化形成有关，然而，在日本尚未研究遗传变异的影响。在本研究中，我们通过直接测序鉴定了clusterin基因的11个单核苷酸多态性（SNP）。他们之中。对 525 名未接受降脂药物治疗的无症状高血压患者进行了 1 个启动子 SNP（-4453T > G）、1 个错义 SNP（41836 > A）和 2 个常见 SNP（5608T > C 和 6316delT）的基因分型。 -4453T>G、41836>A和5608T>C与临床特征没有相关性，然而，在6316delT中，插入(1)/缺失(D)多态性，D/D受试者的总胆固醇和低密度脂蛋白(LDL)胆固醇水平显着高于女性中的I/I受试者，但男性中没有。具有 D 等位基因 (D/D + 1/D) 的女性受试者比 I/I 受试者的颈动脉内膜中层厚度更大。在多重逻辑回归分析中，检测到 6316delT 的 D 等位基因是斑块患病率的独立预测因子。总之，簇蛋白基因多态性可能与日本女性高血压患者的血脂水平和颈动脉粥样硬化的进展有关。 (c) 2005 Elsevier Inc. 保留所有权利。
Clusterin has been implicated in lipid metabolism and atherogenesis, however, the influence of genetic variation has not been examined in Japanese. In this study, we identified 11 single nucleotide polymorphisms (SNPs) of clusterin gene by direct sequencing. Among them. one promoter SNP (-4453T > G), one missense SNP (41836 > A), and 2 common SNPs (5608T > C and 6316delT) were genotyped in 525 asymptomatic hypertensives not treated with lipid lowering agents. -4453T > G, 41836 > A, and 5608T > C showed no correlation with the clinical characteristics, however, in the 6316delT, an insertion (1)/deletion (D) polymorphism, D/D subjects had significantly higher levels of total cholesterol and low-density lipoprotein (LDL)-cholesterol than I/I subjects in females but not in males. Female subjects with the D allele (D/D + 1/D) had greater intima-media thickness of the carotid artery than I/I subjects. In a multiple logistic regression analysis, the D allele of 6316delT was detected as an independent predictor for the plaque prevalence. In conclusion, the clusterin gene polymorphism may contribute to the serum lipid levels and the progression of carotid atherosclerosis in hypertensive Japanese females. (c) 2005 Elsevier Inc. All rights reserved.