2型糖尿病患者转录因子7类似物2基因多态性与瑞格列奈及罗格列酮疗效的关系

Relationship between transcription factor 7-like 2 gene polymorphism and effects of repaglinide and rosiglitazone in patients with type 2 diabetes

目的研究转录因子7类似物2(TCF7L,2)基因多态性与2型糖尿病患者口服瑞格列奈及罗格列酮疗效之间的相关性。方法选取新诊断的2型糖尿病患者209例,随机分为2组,分别接受瑞格列奈(104例)或罗格列酮(105例)单药治疗48 wk。检测治疗前后人体基本参数及糖、脂代谢相关指标,以及TCF7L2基因rs7903146变异。并分析不同基因型患者这2种药物的疗效有无差异。结果 209例患者中完成48 wk随访168例,已知基因型189例,其中CC、CT、TT基因型频率分别为92.6%(175例),6.9%(13例),0.5%(1例)。治疗48 wk后,瑞格列奈组CT+TT基因型患者糖化血红蛋白改善程度优于CC型患者(P<0.05)。罗格列酮组CC基因型患者的空腹胰岛素水平和胰岛素抵抗指数高于CT+TT基因型患者,差异有显著意义(P<0.05),其余指标各基因型间均无显著差异(P>0.05)。结论 TCF7L2基因rs7903146变异与瑞格列奈治疗2型糖尿病的疗效相关,T等位基因型携带者对瑞格列奈的反应优于CC基因型携带者。未发现这一位点变异与罗格列酮的疗效相关。

AIM To investigate the relationship between the genetic polymorphism of the transcription factor 7-like 2(TCF7L2)gene and the effects of repaglinide and rosiglitazone in patients with type 2 diabetes. METHODS A total of 209 newly diagnosed type 2 diabetic patients were recruited and randomly assigned into two groups.The patients were respectively treated with repaglinide(104 patients)or rosiglitazone(105 patients) for 48 weeks.Anthropometric parameters and indices related to glucose and lipid metabolism were tested before and after the treatment.All patients were genotyped for TCF7L2 rs7903146 by Sequenom.RESULTS Among the 209 patients,168 patients completed the 48-week follow-up visit and 189 patients were known genetypes.The frequencies of CC,CT and TT genetypes were 92.6%,6.9%and 0.5%,respectively.After 48-week treatment, glycosylated hemoglobin A_(1c)improvement of T allele carrier was better than that of CC genotype in the repaglinide group(P<0.05).There was significant difference in fasting insulin level and insulin resistance between CC genotype and T allele carrier in the rosiglitazone group(P<0.05),while other parameter differences showed no significant relationship(P>0.05).CONCLUSION Variation of rs7903146 in TCF7L2 is associated with the response to repaglinide treatment in patients with type 2 diabetes.The effect of repaglinide in T allele carriers is better than that in CC homozygotes.However,the association between this variation and rosiglitazone is not found.