Ser 1369Ala variant in sulfonylurea receptor gene ABCC8 Is associated with antidiabetic efficacy of gliclazide in Chinese Type 2 diabetic patients

Yan Feng, Guangyun Mao, Xiaowei Ren, Houxun Xing, Genfu Tang, Qiang Li, Xueqi Li, Lirong Sun, Jinqui Yang, Weiqing Ma, Xiaobin Wang, Xiping Xu

Research output: Contribution to journalArticle

Abstract

OBJECTIVE - The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS- A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates. RESULTS- After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/1 at baseline to 7.7 mmol/1. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Serl369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Serl369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P <0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide. CONCLUSIONS- In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Serl369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.

Original languageEnglish (US)
Pages (from-to)1939-1944
Number of pages6
JournalDiabetes Care
Volume31
Issue number10
DOIs
Publication statusPublished - Oct 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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