Analysis of the Type 2 Diabetes-Associated Single Nucleotide Polymorphisms in the Genes IRS1, KCNJ11, and PPARG2 in Type 1 Diabetes
- Christina Eftychi1,
- Joanna M.M. Howson1,
- Bryan J. Barratt1,
- Adrian Vella1,
- Felicity Payne1,
- Deborah J. Smyth1,
- Rebecca C.J. Twells1,
- Neil M. Walker1,
- Helen E. Rance1,
- Eva Tuomilehto-Wolf2,
- Jaakko Tuomilehto23,
- Dag E. Undlien4,
- Kjersti S. Rønningen5,
- Cristian Guja6,
- Constantin Ionescu-Tı̂irgovişte6,
- David A. Savage7 and
- John A. Todd1
- 1Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K
- 2Diabetes and Genetic Epidemiology Unit, National Public Health Institute, University of Helsinki, Helsinki, Finland
- 3Department of Public Health, University of Helsinki, Helsinki, Finland
- 4Institute of Medical Genetics, Ulleval University Hospital, University of Oslo, Oslo, Norway
- 5Laboratory of Molecular Epidemiology, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
- 6Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
- 7Department of Medical Genetics, Queen’s University Belfast, Belfast City Hospital, Belfast, Northern Ireland
- Address correspondence and reprint requests to John A. Todd, JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Rd., Cambridge CB2 2XY, U.K. E-mail: john.todd{at}cimr.cam.ac.uk
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.
- ICAM1, intercellular adhesion molecule 1
- IRS1, insulin receptor substrate 1
- KCNJ11, potassium inwardly rectifying channel gene
- PPARγ, peroxisome proliferator-activated receptor γ
- PPARG2, peroxisome proliferator-activated receptor γ2 gene
- SNP, single nucleotide polymorphism
- TDT, transmission/disequilibrium test
Footnotes
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- Accepted October 31, 2003.
- Received October 3, 2003.
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