Ser1369Ala variant in sulphonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients
- Yan Feng, MD, PhD1,
- Guangyun Mao, MD, PhD1,
- Xiaowei Ren, MD1,
- Houxun Xing, MD1,
- Genfu Tang, MD1,
- Qiang Li, MD, PhD2,
- Xueqi Li, MD3,
- Lirong Sun, MD4,
- Jinqui Yang, MD, PhD5,
- Weiqing Ma, MD6,
- Xiaobin Wang, MD, ScD7 and
- Xiping Xu, MD, PhD (xipingxu18{at}gmail.com)1
- 1 Anhui Biomedical Institute, Anhui Medical University, Hefei, China
- 2 Division of Endocrinology, the Second Hospital, Harbin Medical University, Harbin, China
- 3 Division of Endocrinology, the First Hospital, Harbin Medical University, Harbin, China
- 4 Tianjin Medical University Metabolic Hospital, Tianjin, China
- 5 Division of Endocrinology, Tongren Hospital, Capital Medical University, Beijing, China
- 6 Division of Endocrinology, the First Hefei People Hospital, Hefei, China
- 7 The Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL USA
Abstract
Objective- To investigate if genetic variants could influence antidiabetic efficacy of gliclazide in type 2 diabetes (T2D) patients.
Research design and methods- 1268 T2D patients, who were diagnosed within the past 5 years and had no recent hypoglycemic treatment, were enrolled from 23 hospitals in China. All the patients were treated with gliclazide for 8 weeks. Fasting and OGTT 2 hour plasma glucose (PG), fasting insulin, and HbA1c were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms (SNP) in11 candidate genes with antidiabetic efficacyof gliclazide. General linear regression model was performed to test the association with adjustment for important covariates.
Results- After 8 weeks of gliclazide therapy, mean FPG was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all the 25 SNPs (N=661) and found that Ser1369Ala of ABCC8 gene and rs5210 of KCNJ11 gene, were significantly associated with FPG decrease (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 to subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotypes had 7.7% greater decrease in FPG (P<0.001), 11.9% greater decrease in 2 hour PG (P=0.003) and 3.5% greater decrease in HbA1c (P=0.06) after 8 weeks treatment with gliclazide.
Conclusions- In two independent cohorts of Chinese T2D patients, we found consistent evidence that Ser1369Ala variant in ABCC8 gene can influence antidiabetic efficacy of gliclazide.
Footnotes
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- Received November 26, 2007.
- Accepted June 21, 2008.
- Copyright © American Diabetes Association
