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.

• Authors: Tao Wang, Yan Wang, Dong-Mei Lv, Jin-Fang Song, Qian Lu, Xing Gao, Fan Zhang, Hao Guo, Wei Li, Xiao-Xing Yin
• Journal: Pharmacotherapy (Pharmacotherapy) Vol. 34 Issue 2 Pg. 131-9 (Feb 2014) ISSN: 1875-9114 [Electronic] United States
• PMID: 24338736 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Pharmacotherapy Publications, Inc.

Chemical References

• Adaptor Proteins, Signal Transducing
• Blood Glucose
• Carbamates
• Hypoglycemic Agents
• NOS1AP protein, human
• Piperidines
• repaglinide

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Adult
• Alleles
• Asian People (genetics)
• Blood Glucose (drug effects)
• Carbamates (therapeutic use)
• Case-Control Studies
• Diabetes Mellitus, Type 2 (drug therapy, genetics)
• Female
• Gene Frequency
• Genotype
• Humans
• Hypoglycemic Agents (therapeutic use)
• Male
• Middle Aged
• Piperidines (therapeutic use)
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Polymorphism, Restriction Fragment Length
• Prospective Studies