影响他汀类药物降脂治疗的相关基因的多态性及其与高脂血症的关系

Correlation of genetic polymorphism with statins therapy and hyperlipidemias

目的观察他汀类药物降脂治疗相关的基因多态性位点CYP3A4*1G、CYP3A 5*3、MDRl C3435T、SLC21A6 A388G、SLC21A6 T521C、CYP7Al A-204C及ABCG8 T400K在河南地区的分布及其与高脂血症的关系。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)和等位基因特异性-聚合酶链式反应(AS-PCR)技术对400名高脂血症病人和320名正常对照者进行基因分型。结果等位基因SLC21A6 A388G、SLC21A6 T521C、CYP3A4*1G、CYP3A5*3、MDR1 C3435T、CYP7A1 A-204C及ABCG8 400K的分布频率在高脂血症病人中分别为72.1%、16.2%、27.9%、73.7%、39.9%、34.7%和12.8%,在正常对照组中分别为71.5%、16.1%、27.4%、74.5%、39.4%、33.3%和7.4%;ABCG8 400K等位基因携带者患高脂血症的风险显著增加(OR=1.870,CI:1.259-2.777,P=0.002)。结论CYP3A5*3、MDR1 C3435T、SLC21A6 A388G、SLC21A6 T521C和ABCG8 T400K基因多态性分布可能存在地区或种族差异,ABCG8 400K等位基因是高脂血症的高风险因素。

AIM To investigate the distribution of genetic polymorphisms alleles： CYP3A4＊1G, CYP3A5＊3, MDR1 C3435T, SLC21A6 A388G, SLC21A6 T521C, CYP7A1 A-204C and A BCG8 T400K correlated to statins therapy in patients with hyperlipidemia of He-nan area. METHODS Genotypes were determined by using Polymerase Chain Reaction-Restrict Fragment Length Polymorphism （PCR-RFLP） and Allele-Specific Polymerase-Chain Reaction （AS-PCR） in 400 hyperlipidemia patients and 320 healthy controls. RESULTS The distribution frequencies of allele of SLC21A6 A388G, SLC21A6 T521C, CYP3A4＊1G, CYP3A5＊3, MDR1 C3435T, CYP7A1 A-204C and A BCG8 T400K were 72.1%, 16.2 %, 27.9 %, 73.7 %, 39.9 %, 34.7 %, 12.8 %in hyperlipidemia patients and 71.5 %, 16.1%, 27.4 %, 74.5 %, 39.4 %, 33.3 %, 7.4 % in controls, respectively. Subjects with A BCG8 400K allele had higher risk of hyperlipidemia （OR = 1.870, CI： 1.259- 2.777, P = 0.002）. CONCLUSION These data suggest that the distribution of gene polymorphisms of CYP3A5＊3, SLC21A6 A388G, MDR1 C3435T, SLC21A6 T521C and A BCG8 T400K may possess variance with specific area and ethnic population, A BCG8 400K allele gene shows high risk of hyperlipemia.