Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients
Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients
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DOI：
10.1111/j.1745-7254.2008.00840.x
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发表时间：
2008-08-01
影响因子：
8.2
通讯作者：
Xiang, Kunsan
中科院分区：
文献类型：
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作者：
He, Ya-yi;Zhang, Rong;Xiang, Kunsan
目的：本研究旨在探讨KCNJ 11 E23 K和ABCC 8外显子16 - 3 T/C与瑞格列奈治疗2型糖尿病疗效的关系。方法：100例新诊断的2型糖尿病患者接受瑞格列奈治疗24周。进行精氨酸刺激试验以评价β细胞功能。PCR-限制性片段长度多态性检测基因变异。应答者定义为瑞格列奈治疗24周后空腹血糖降低25%以上或血红蛋白A1 c（HbA 1c）值降低20%以上（或两者）。结果如下：与E/E纯合子相比，KCNJ 11 E23 K变异体E/K和K/K基因型患者的基线HbA 1c和HbA 1c下降均显著更高（P分别为0.0103和0.0221）。E/K杂合子的餐后2 h血糖（2 hPG）下降幅度显著大于E/E纯合子（P=0.0367）。E和K等位基因对瑞格列奈治疗的应答率有显著差异（68% vs 82%，P=0.0324）。ABCC 8外显子16 -3 C/C基因型患者的空腹胰岛素变化和胰岛素抵抗的稳态模型评估值显著高于T/C和T/T基因型患者（P分别为0.0372和0.0274）。结论：KCNJ 11 E23 K变异与瑞格列奈的疗效相关。此外，ABCC 8外显子16 - 3 T/C变异的C/C纯合子对瑞格列奈的胰岛素敏感性优于T/C和T/T基因型。
Aim: The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes. Methods: A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment. Results: Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P=0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P=0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16-3 C/C versus the T/C and T/T genotypes (P=0.0372 and 0.0274, respectively). Conclusion: The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.