CYP7A1 多态性对非诺贝特降脂反应的影响。
The effect of CYP7A1 polymorphisms on lipid responses to fenofibrate.
机构信息
Bone and Mineral Unit, Division of Endocrinology, Oregon Health and Science University, Portland, OR 97239, USA.
出版信息
J Cardiovasc Pharmacol. 2012 Mar;59(3):254-9. doi: 10.1097/FJC.0b013e31823de86b.
INTRODUCTION
CYP7A1 encodes cholesterol 7α-hydroxylase, an enzyme crucial to cholesterol homeostasis. Its transcriptional activity is downregulated by fenofibrate. The goal of this study was to determine the effect of CYP7A1 polymorphisms on lipid changes in response to fenofibrate.
METHODS
We examined the associations of 3 tagging single nuclear polymorphisms (i6782C>T, m204T>G, 3U12536A>C) at CYP7A1 with triglyceride (TG) and high-density lipoprotein cholesterol (HDL)-C responses to a 3-week treatment with 160 mg/d of fenofibrate in 864 US white participants from the Genetics of Lipid Lowering Drugs and Diet Network study.
RESULTS
The m204T>G variant was significantly associated with TG and HDL-C responses with fenofibrate. Individuals homozygous for the common T allele of m204T>G single nuclear polymorphism displayed both the greater reduction of TG (-32% for TT, -28% for GT, -25% for GG, P = 0.004) and an increase of HDL-C response compared with noncarriers (4.1% for TT, 3.4% for GT, 1.2% for GG, P = 0.01). Conversely, individuals homozygous for the minor allele of i6782C>T showed a greater increase in the HDL-C response compared with noncarriers (2.8% CC, 4.5% for CT, 5.8% for TT, P = 0.02), albeit no significant effect on TG response.
CONCLUSIONS
Our data suggest that common variants at the CYP7A1 locus modulate the TG-lowering and HDL-C-raising effects of fenofibrate, and contribute to the interindividual variation of the drug responses.
简介
CYP7A1 编码胆固醇 7α-羟化酶，是胆固醇动态平衡的关键酶。其转录活性被非诺贝特下调。本研究的目的是确定 CYP7A1 多态性对非诺贝特引起的脂质变化的影响。
方法
我们研究了 3 个位于 CYP7A1 的标签单核苷酸多态性（i6782C>T、m204T>G、3U12536A>C）与美国遗传学降脂药物和饮食网络研究中 864 名美国白种人参与者接受 160mg/d 非诺贝特治疗 3 周后甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）反应的相关性。
结果
m204T>G 变体与非诺贝特治疗后 TG 和 HDL-C 的反应显著相关。m204T>G 单核苷酸多态性常见 T 等位基因纯合子个体的 TG 降低幅度更大（TT 为-32%，GT 为-28%，GG 为-25%，P=0.004），与非携带者相比 HDL-C 反应增加（TT 为 4.1%，GT 为 3.4%，GG 为 1.2%，P=0.01）。相反，i6782C>T 的少数等位基因纯合子个体的 HDL-C 反应增加幅度大于非携带者（CC 为 2.8%，CT 为 4.5%，TT 为 5.8%，P=0.02），但对 TG 反应无显著影响。
结论
我们的数据表明，CYP7A1 基因座的常见变异体调节非诺贝特的降低 TG 和升高 HDL-C 的作用，并导致药物反应的个体间差异。
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