A Variation in the ABCC8 Gene Is Associated with Type 2 Diabetes Mellitus and Repaglinide Efficacy in Chinese Type 2 Diabetes Mellitus Patients

Abstract

Objective Previous studies have suggested that variations in the ABCC8 gene may be closely associated with T2DM susceptibility and repaglinide response. However, these results have not been entirely consistent, and there are no related studies in a Chinese population, suggesting the need for further exploration. The current study investigated the associations of the ABCC8 rs1801261 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. Methods A total of 234 T2DM patients and 105 healthy subjects were genotyped for ABCC8 rs1801261 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism assay. A total of 70 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take 3 mg repaglinide per day (1 mg each time before meals) for 8 consecutive weeks. The pharmacodynamic parameters of repaglinide and biochemical indicators were then determined before and after repaglinide treatment. Results The frequency of ABCC8 rs1801261 allele was higher in T2DM patients than in the control subjects (22.6% vs.11.0%, p<0.01). After repaglinide treatment, T2DM patients carrying genotype CT showed a significantly attenuated efficacy on FPG (p<0.01) and HbA1c (p<0.01) compared with those with genotype CC. Conclusion These results suggested that the ABCC8 rs1801261 polymorphism might influence T2DM susceptibility and the therapeutic effect of repaglinide in Chinese Han T2DM patients. This study was registered in the Chinese Clinical Trial Register on May 14, 2013 (No. ChiCTR-CCC13003536).

Keywords: ABCC8; gene polymorphism; insulin secretion; repaglinide; sulfonylurea receptor 1; type 2 diabetes mellitus.

Figure.

Changes in FPG and HbA1c in T2DM patients after treatment with repaglinide. Changes in fasting blood glucose (FPG; post-administration levels minus pre-administration levels) and glycated hemoglobin (HbA1c; post-administration levels minus pre-administration levels) in type 2 diabetes mellitus patients with different ABCC8 rs1801261 genotypes after treatment with repaglinide. Data are expressed as the mean with the standard error of the mean (n=70). *p<0.05, **p<0.01 compared with the CC genotype group.