Analysis of the Type 2 Diabetes-Associated Single Nucleotide Polymorphisms in the Genes IRS1, KCNJ11, and PPARG2 in Type 1 Diabetes

Author:

Eftychi Christina1,Howson Joanna M.M.1,Barratt Bryan J.1,Vella Adrian1,Payne Felicity1,Smyth Deborah J.1,Twells Rebecca C.J.1,Walker Neil M.1,Rance Helen E.1,Tuomilehto-Wolf Eva2,Tuomilehto Jaakko23,Undlien Dag E.4,Rønningen Kjersti S.5,Guja Cristian6,Ionescu-Tı̂irgovişte Constantin6,Savage David A.7,Todd John A.1

Affiliation:

1. Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K

2. Diabetes and Genetic Epidemiology Unit, National Public Health Institute, University of Helsinki, Helsinki, Finland

3. Department of Public Health, University of Helsinki, Helsinki, Finland

4. Institute of Medical Genetics, Ulleval University Hospital, University of Oslo, Oslo, Norway

5. Laboratory of Molecular Epidemiology, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway

6. Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania

7. Department of Medical Genetics, Queen’s University Belfast, Belfast City Hospital, Belfast, Northern Ireland

Abstract

It has been proposed that type 1 and 2 diabetes might share common pathophysiological pathways and, to some extent, genetic background. However, to date there has been no convincing data to establish a molecular genetic link between them. We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly972Arg in the insulin receptor substrate 1 (IRS1) gene, Glu23Lys in the potassium inwardly-rectifying channel gene (KCNJ11), and Pro12Ala in the peroxisome proliferative-activated receptor γ2 gene (PPARG2). We were unable to confirm a recently published association of the IRS1 Gly972Arg variant with type 1 diabetes. Moreover, KCNJ11 Glu23Lys showed no association with type 1 diabetes (P > 0.05). However, the PPARG2 Pro12Ala variant showed evidence of association (RR 1.15, 95% CI 1.04–1.28, P = 0.008). Additional studies need to be conducted to confirm this result.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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