Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients

  1. Yan Feng, MD, PHD1,
  2. Guangyun Mao, MD, PHD1,
  3. Xiaowei Ren, MD1,
  4. Houxun Xing, MD1,
  5. Genfu Tang, MD1,
  6. Qiang Li, MD, PHD2,
  7. Xueqi Li, MD3,
  8. Lirong Sun, MD4,
  9. Jinqui Yang, MD, PHD5,
  10. Weiqing Ma, MD6,
  11. Xiaobin Wang, MD, SCD7 and
  12. Xiping Xu, MD, PHD1
  1. 1Anhui Biomedical Institute, Anhui Medical University, Hefei, China
  2. 2Division of Endocrinology, the Second Hospital, Harbin Medical University, Harbin, China
  3. 3Division of Endocrinology, the First Hospital, Harbin Medical University, Harbin, China
  4. 4Tianjin Medical University Metabolic Hospital, Tianjin, China
  5. 5Division of Endocrinology, Tongren Hospital, Capital Medical University, Beijing, China
  6. 6Division of Endocrinology, the First Hefei People's Hospital, Hefei, China
  7. 7The Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, Illinois
  1. Corresponding author: Xiping Xu, xipingxu18{at}gmail.com

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/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala 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 Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 3 July 2008.

    Y.F. and G.M. contributed equally to this study.

    Y.F. is currently affiliated with Bridgeport Hospital, Yale University School of Medicine, New Haven, Connecticut.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted June 21, 2008.
    • Received November 26, 2007.
| Table of Contents

This Article

  1. Diabetes Care vol. 31 no. 10 1939-1944
  1. All Versions of this Article:
    1. dc07-2248v1
    2. 31/10/1939 most recent