有机阴离子转运多肽OATP1B1基因多态性与瑞格列奈药物疗效的相关性研究

Correlation Between Gene Polymorphism of Organic Anion Transport Polypeptide OATP1B1 and Drug Efficacy of Repaglinide

目的探讨有机阴离子转运多肽OATP1B1基因多态性与瑞格列奈药物疗效的相关性。方法筛选医院2014年3月至2016年3月收治的2型糖尿病患者45例,入组患者均常规口服瑞格列奈片3个月,检测OATP1B1 OATP1B1 388A> G(rs2306282),OATP1B1521T> C(rs41409056)多态性及治疗前后糖、脂代谢相关指标变化。结果 A,G等位基因频率分别为67. 78%和32. 22%; T,C等位基因频率分别为84. 44%和15. 56%,不符合Hardy-Weinberg平衡定律,仅分析OATP1B1 388A> G与瑞格列奈药物疗效的相关性。使用瑞格列奈药物治疗后,AA,AG,GG 3组进行对比分析,AA组空腹血糖(FBG)和糖化血红蛋白(HbA1C)均有显著改善(P <0. 05),AG组仅有HbA1C显著改善(P <0. 05),GG组FBG等相关指标均无显著改善(P> 0. 05);治疗后,GG组总胆固醇(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)改善最显著,且优于其他组(P <0. 05)。结论 OATP1B1 OATP1B1 388A> G(rs2306282)位点变异与瑞格列奈药物治疗2型糖尿病的疗效无明显相关性,但其位点变异与脂代谢指标变化相关,其中GG组脂代谢指标下降最显著。

To investigate the correlation between gene polymorphism of organic anion transporter polypeptide（OATP1B1） and drug efficacy of repaglinide. Methods Totally 45 patients with type 2 diabetes mellitus（T2DM） admitted to our hospital from March 2014 to March 2016 were selected and routinely treated with oral Repaglinide Tablets for 3 months, the polymorphisms of OATP1B1 OATP1B1 388A 〉 G（rs2306282）, OATP1B1 521T 〉 C（rs41409056） and the related indicators of glucose and lipid metabolism were detected before and after treatment. Results The A and G alleles frequencies were 67.78% and 32.22%, the T and C alleles frequencies were 84.44% and 15.56%, which did not meet the Hardy-Weinberg equilibrium law. Therefore this study only analyzed the correlation between OATP1B1 388A 〉 G and drug efficacy of repaglinide. After treatment with repaglinide, the AA, AG and GG three groups were compared and analyzed, and the results showed that the levels of FBG and HbAlc in the AA group were significantly improved （P 〈 0.05）, the level of HbAlc in the AG group was significantly improved（P 〈 0.05）, there was no significant improvement in the levels of related indicators of FBG in the GG group（P 〉 0. 05）. After treatment, the levels of TG, HDL-C and LDL-C in the GG group were significantly improved, and the improvement in the GG group was better than that in the other two groups（P 〈 0.05）. Conelusion Variation of OATP1B1 0ATP1B1 388A 〉 G（rs2306282） locus has no significant correlation with the efficacy of repaglinide in the treatment of T2DM, but the locus variation is related to the changes of lipid metabolism indexes, and the lipid metabolism indexes are decreased most significantly in the GG group.