中国汉族人群中 KCNQ1基因多态性与2型糖尿病的相关性研究及对吡格列酮疗效的影响

摘要

Objective To investigate whether the KCNQ1 (potassium voltage-gated channel,KQT-like subfamily,member 1 )gene rs2237897 polymorphism was associated with T2DMand pioglitazone efficacy in Chinese Han T2DMpatients.Methods A total of 321 T2DM patients and 345 healthy volunteers were enrolled to identify KCNQ1 gene rs2237897 polymorphism by polymerase chain reaction-restriction fragment length polymorphism assay.Fifty-one patients with CYP2C8*1*1 genotype were selected and given a 12-week pioglitazone treat-ment (30 mg /d).Fasting plasma glucose (FPG),postprandial plasma glucose (PPG),glycated hemoglobin (HbAlc),serum triglycerides (TG),total cholesterol (TC),low-density lipoprotein-cholesterol (LDL-c)and high-density lipoprotein-cholesterol (HDL-c)were deter-mined before and after pioglitazone treatment.Results KCNQ1 gene rs2237897 polymorphism was associated with T2DMin Chinese (OR=1.918,95% CI 1.113-3.075,P<0.05).The pioglitazone efficacy on DVPPG(differential value post prandial plasma glucose)(P<0.05) and DVPINS (differential value postprandial serum insulin)were lower in patients with rs2237897 CT+TT genotypes compared with CC geno-type carriers.Conclusions KCNQ1 gene rs2237897 polymorphism is associated with T2DM and pioglitazone therapeutic efficacy in Chinese Han population.%目的：探讨中国2型糖尿病（T2DM）患者中KCNQ1基因rs2237897多态性与T2DM的相关性及对吡格列酮疗效的影响。方法本研究采用病例-对照研究模式。使用聚合酶链反应-限制性片段长度多态（PCR-RFLP）方法对321例T2DM患者和345名健康对照者进行KCNQ1（potassium voltage-gated channel，KQT-like subfamily，member 1）基因rs2237897位点分型；选择51例患者给予连续12周每天30 mg吡格列酮治疗。检测计算体重指数（BMI）、空腹血糖（FPG）、餐后血糖（PPG）、空腹胰岛素（FINS）、餐后胰岛素（PINS）、糖化血红蛋白（HbAlc）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-c）和高密度脂蛋白胆固醇（HDL-c）等指标。结果 KCNQ1基因rs2237897多态性与T2DM相关（OR＝1．918，95％ CI 1．113-3．075，P＜0．05）。携带KC-NQ1基因rs2237897 CT＋TT基因型患者经吡格列酮治疗12周后的PPG （mmol/L）（DV -0．79±3．96 vs -2．75±3．8，P＜0．05）下降值和DVPINS （mU/L）（DV 14．08±16．82 vs 28．69±19．11，P＜0．05）增加值均显著低于野生CC基因型患者。结论中国汉族人群中KCNQ1基因rs2237897多态性与T2DM的易感性相关并影响吡格列酮的疗效。