Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus

Abstract

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.

Keywords: NOS1AP rs12742393; genetic polymorphism; repaglinide; type 2 diabetes mellitus.