转录因子2基因单核苷酸多态性对瑞格列奈和罗格列酮疗效的影响

Effects of single nucleotide polymorphism of transcription factor 2 on efficiency of repaglinide and rosiglitazone: a clinical report of 209 cases

摘要:

目的 研究转录因子2（TCF2）基因多态性与新诊断2型糖尿病患者服用瑞格列奈或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例并随机分配到瑞格列奈治疗组（104例）和罗格列酮治疗组（105例），单药治疗48周，测量治疗前后人体基本参数及糖脂代谢相关指标，以及TCF2基因rs4430796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 （1）209例患者中完成48周随访181例，其中AA、GA、GG基因型频率分别为50.2%，39.2%，10.6%。（2）罗格列酮治疗组，TCF2不同基因型患者在基线时的空腹胰岛素及胰岛β细胞功能指数有显著差异。（3）罗格列酮组不同基因型患者在治疗24及48周后精氨酸刺激试验一相胰岛素分泌反应存在显著差异。（4）经瑞格列奈治疗24周之后，不同基因型患者空腹胰岛素及胰岛素敏感性指数较基线时的改善存在显著差异。结论 TCF2基因rs4430796变异与罗格列酮及瑞格列奈治疗2型糖尿病的疗效相关。

Abstract:

Objective To investigate the relationship of transcription factor 2 (TCF2) gene polymorphism with the efficiency of repaglinide or rosiglitazone in the patients with newly-diagnosed type 2 diabetes mellitus (T2DM). Methods A total of 209 newly-diagnosed T2DM patients were prospectively recruited in this study. They were randomly assigned into 2 groups, and were treated with repaglinide (n＝104) and rosiglitazone (n＝105) for 48 consecutive weeks respectively. Anthropometric parameters and indices related to glucose and lipid metabolism were tested before and after the treatment. All patients were genotyped for TCF2 rs4430796 by Sequenom. The efficiency of the 2 drugs were analyzed in the patients with different genotypes. Results Among the 209 patients, 181 of them completed the 48-week follow-up. Their frequencies of AA, GA and GG genotypes were 50.2%, 39.2% and 10.6%, respectively. In the rosiglitazone cohort, there were significant differences in fasting insulin levels and HOMA-β scores at baseline (for assessment of beta-cell functionality) among the 3 genotype groups. After 24- or 48-week treatment, arginine stimulation test showed that significant differences were seen in acute insulin response (AIR) among the 3 genotype groups in the patients treated by rosiglitazone (P＜0.05). For the repaglinide cohort, there were significant differences in the fasting insulin levels and HOMA-IR among the 3 genotype groups after 24 weeks’ treatment. Conclusion Variation of rs4430796 in TCF2 is associated with the response to rosiglitazone or repaglinide treatment in the patients with type 2 diabetes.