CETP基因启动子区多态与他汀类药物调血脂效果的关联分析

The Association Between CETP Gene Promoting Polymorphisms with the Lipid-Regulating Effects of Statins

目的探讨胆固醇酯转运蛋白基因启动子区-69G/A、-629C/A、-971G/A和-1337C/T单核苷酸多态性与他汀类药物调血脂效果的关系。方法采用聚合酶链反应-限制性片段长度多态方法检测207例经辛伐他汀调脂治疗的血脂异常患者胆固醇酯转运蛋白基因4个多态性位点的基因型频率分布情况,并比较各项血脂水平的改变量在各多态位点基因型之间的差异。结果 -69G/A多态未检出A等位基因;辛伐他汀治疗后,总胆固醇和低密度脂蛋白胆固醇水平的改变量在-629C/A多态各基因型组间差异均有显著性(P=0.025;P=0.000),-629AA基因型个体的总胆固醇水平下降幅度较CC基因型个体要高出0.495 mmol/L(P=0.020),-629AA和CA基因型个体中的低密度脂蛋白胆固醇水平下降幅度比CC基因型个体分别高出0.577 mmol/L和0.352 mmol/L(P=0.000,P=0.012);高密度脂蛋白胆固醇水平的改变量在-1337C/T多态各基因型组间差异有显著性(F=3.064,P=0.044),高密度脂蛋白胆固醇水平升高的幅度在-1337TT、TC和CC基因型组间有逐渐增大的趋势;各项血脂水平的改变量在-971G/A多态3种基因型组间的差异无统计学意义。结论 -629C/A多态和-1337C/T多态与他汀类药物调血脂效果有关联。

Aim To investigate the association between the lipid-regulating effect of statins with the CETP-69G/A,-629C/A,-971G/A and-1337C/T polymorphisms. Methods The target DNA fragments of CETP gene were amplified and analyzed by PCR-RFLP technique in 207 dyslipidemia patients treated with statins.The relationship between each SNP and each blood-fat index was analyzed by SPSS statistic software. Results The A allele was not found in the-69G/A polymorphism;After the treatment with simvastatin,the TC and LDLC decreasing extent were significantly different（P=0.025;P=0.000）between-629C/A genotypes,respectively.The-629AA individuals were 0.495 mmol/L（P=0.020）higher than CC individuals in TC decreasing extent.The LDLC decreasing extent were 0.577 mmol/L and 0.352 mmol/L（P=0.000,P=0.012） higher in-629AA and CA individuals than CC individuals;the-1337C/T polymorphisms was associated with the rising extent of HDLC level（F=3.064,P=0.044）.The HDLC rising extent was gradually increased among-1337TT,TA and AA genotypes.There was no significant difference in the change of blood fat level between the-971G/A genotypes after the treatment with simvastatin. Conclusion The-629C/A and-1337C/T polymorphisms were associated with the lipid-regulating effect of statins.