一氧化氮合酶1衔接蛋白（NOS1AP）基因rs12742393多态性对中国2型糖尿病患者瑞格列奈反应的影响。
Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus.
作者信息
Wang Tao, Wang Yan, Lv Dong-Mei, Song Jin-Fang, Lu Qian, Gao Xing, Zhang Fan, Guo Hao, Li Wei, Yin Xiao-Xing
机构信息
Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou, China; Department of Pharmacy, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
出版信息
Pharmacotherapy. 2014 Feb;34(2):131-9. doi: 10.1002/phar.1379. Epub 2013 Dec 13.
STUDY OBJECTIVE
To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM.
DESIGN
Prospective case-control study.
SETTING
Academic medical center.
PATIENTS
A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks.
MEASUREMENTS AND MAIN RESULTS
Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers.
CONCLUSION
The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients.
研究目的
探讨一氧化氮合酶1衔接蛋白（NOS1AP）基因rs12742393多态性与中国2型糖尿病（T2DM）患者2型糖尿病发病风险及瑞格列奈治疗效果的相关性。
设计
前瞻性病例对照研究。
研究地点
学术医疗中心。
患者
共纳入300例T2DM患者和200名健康志愿者，采用聚合酶链反应-限制性片段长度多态性分析确定NOS1AP rs12742393基因型。随机选取84例不同基因型患者接受口服瑞格列奈单药治疗（3毫克/天），疗程8周。
测量指标及主要结果
在瑞格列奈治疗前后进行人体测量及空腹血糖（FPG）、餐后血糖、糖化血红蛋白、空腹血清胰岛素（FINS）、餐后血清胰岛素、胰岛素抵抗稳态模型评估（HOMA-IR）、甘油三酯、总胆固醇、低密度脂蛋白胆固醇及高密度脂蛋白胆固醇检测。T2DM患者中NOS1AP rs12742393风险C等位基因频率高于健康志愿者（p<0.001）。与基因型CC的T2DM患者相比，NOS1AP rs12742393基因型为AA和AC的T2DM患者FPG（毫摩尔/升）显著降低（p<0.01）。CC纯合子和AC杂合子患者的FINS（毫单位/升）升高幅度大于野生型AA患者（p<0.05）。此外，与基因型AC和AA携带者相比，NOS1AP rs12742393基因型为CC的携带者HOMA-IR差值更高（p<0.001）。与AA基因型携带者相比，携带NOS1AP rs12742393风险C等位基因的T2DM患者，瑞格列奈治疗对FPG（p<0.01）、FINS（p<0.05）和HOMA-IR（p<0.001）的疗效降低。
结论
NOS1AP rs12742393多态性与瑞格列奈在中国T2DM患者中的治疗效果相关。
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