Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, People's Republic of China.
Eur J Clin Pharmacol. 2010 Dec;66(12):1207-15. doi: 10.1007/s00228-010-0882-6. Epub 2010 Aug 31.
Genome-wide association studies (GWASs) identified that SLC30A8 genetic polymorphism was a risk of type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients.
We conducted a case-control study of 443 T2DM patients and 229 healthy volunteers to identify SLC30A8 rs13266634 and rs16889462 genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-eight patients were randomly selected and underwent an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c) and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment.
SLC30A8 rs13266634 risk C allele frequency was higher in T2DM patients than in healthy controls (P < 0.05). There was a better repaglinide response on FINS (P < 0.05) and PINS (P < 0.01) in patients with rs13266634 CT+TT genotypes compared with CC genotype carriers. Patients with rs16889462 GA genotype showed an enhanced repaglinide efficacy on FPG (P < 0.01), PPG (P < 0.01) and HbAlc (P < 0.05) compared with GG genotype individuals.
SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide therapeutic efficacy in Chinese T2DM patients.
全基因组关联研究（GWAS）发现 SLC30A8 基因多态性是几种人群中 2 型糖尿病（T2DM）的风险因素。本研究旨在探讨 SLC30A8 rs13266634 和 rs16889462 多态性是否与中国 T2DM 患者的 T2DM 易感性和瑞格列奈治疗疗效相关。
我们进行了一项病例对照研究，纳入了 443 例 T2DM 患者和 229 名健康志愿者，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测 SLC30A8 rs13266634 和 rs16889462 基因型。随机选择 48 例患者进行为期 8 周的瑞格列奈治疗（3mg/d）。在瑞格列奈治疗前后测定空腹血糖（FPG）、餐后血糖（PPG）、糖化血红蛋白（HbAlc）、空腹血清胰岛素（FINS）、餐后血清胰岛素（PINS）、胰岛素抵抗评估的稳态模型（HOMA-IR）、血清甘油三酯、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）。
与健康对照组相比，T2DM 患者 SLC30A8 rs13266634 风险 C 等位基因频率更高（P<0.05）。与 CC 基因型携带者相比，rs13266634 CT+TT 基因型患者的 FINS（P<0.05）和 PINS（P<0.01）对瑞格列奈的反应更好。与 GG 基因型个体相比，rs16889462 GA 基因型患者 FPG（P<0.01）、PPG（P<0.01）和 HbAlc（P<0.05）对瑞格列奈的疗效增强。
SLC30A8 rs13266634 和 rs16889462 多态性与中国 T2DM 患者的瑞格列奈治疗疗效相关。
