PPARA 基因的遗传变异与辛伐他汀介导的鹿特丹研究中的胆固醇降低有关。

Genetic variation in the PPARA gene is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study.

机构信息

Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000CA Rotterdam, The Netherlands.

出版信息

Pharmacogenomics. 2013 Aug;14(11):1295-304. doi: 10.2217/pgs.13.112.

DOI:10.2217/pgs.13.112

PMID:23930676

Abstract

AIM

Recently, minor alleles of two strongly linked polymorphisms in the PPARA gene, rs4253728 G>A and rs4823613 A>G, were related to decreased CYP3A4 expression and activity. We studied whether they were associated with the cholesterol-lowering effect of simvastatin.

MATERIALS & METHODS: We identified 123 incident users with cholesterol measurements before and after starting statin therapy in a prospective population-based cohort study. Associations between PPARA polymorphisms and change in total and low-density lipoprotein (LDL)-cholesterol levels were analyzed using linear regression.

RESULTS

The minor G allele of the rs4823613 A>G polymorphism was associated with a 0.258 mmol/l (95% CI: -0.470 to -0.046) and a 0.294 mmol/l (95% CI: -0.495 to -0.093) larger reduction in total and LDL-cholesterol, respectively, after starting simvastatin therapy. Results were similar for the rs4253728 G>A polymorphism.

CONCLUSION

The minor alleles of the PPARA rs4253728 and rs4823613 polymorphisms are associated with a better total and LDL-cholesterol-lowering response to simvastatin, possibly through influence on CYP3A4.

摘要

目的

最近，PPARA 基因中两个紧密连锁的多态性的次要等位基因 rs4253728 G>A 和 rs4823613 A>G，与 CYP3A4 表达和活性降低有关。我们研究了它们是否与辛伐他汀的降胆固醇作用有关。

材料与方法

我们在一项前瞻性基于人群的队列研究中，确定了 123 名开始他汀类药物治疗前和治疗后胆固醇测量的新发病例患者。使用线性回归分析 PPARA 多态性与总胆固醇和低密度脂蛋白（LDL）-胆固醇水平变化之间的关系。

结果

rs4823613 A>G 多态性的次要 G 等位基因与辛伐他汀治疗开始后总胆固醇和 LDL-胆固醇分别降低 0.258 mmol/l（95%CI：-0.470 至 -0.046）和 0.294 mmol/l（95%CI：-0.495 至 -0.093）相关。rs4253728 G>A 多态性的结果相似。