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Exp Clin Endocrinol Diabetes 2007; 115(4): 221-228
DOI: 10.1055/s-2007-970574
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Glutamate Cysteine Ligase Catalytic Subunit Promoter Polymorphisms and Associations with Type 1 Diabetes Age-at-onset and GAD65 Autoantibody Levels

L. M. Bekris 1 , 2 , C. Shephard 2 , 4 , M. Janer 5 , J. Graham 3 , B. McNeney 3 , J. Shin 3 , M. Zarghami 1 , W. Griffith 2 , F. Farin 2 , 4 , T. J. Kavanagh 2 , 4 , A. Lernmark 1
  • 1Department of Medicine, University of Washington, Seattle, WA
  • 2Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA
  • 3Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, B.C., Canada
  • 4UW/NIEHS Center for Ecogenetics and Environmental Health, University of Washington, Seattle, WA
  • 5Institute for Systems Biology, Seattle, WA
Further Information

Publication History

received 4. 11. 2006 first decision 6. 11. 2006

accepted 6. 11. 2006

Publication Date:
03 May 2007 (online)

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Abstract

The purpose of this study was to test the hypothesis that glutamate cysteine ligase catalytic subunit (GCLC) promoter polymorphisms are susceptibility factors for type 1 diabetes (T1D), T1D age-at-onset and T1D autoantibodies. T1D patients and control subjects from the Swedish Childhood Diabetes Registry and the Swedish Diabetes Incidence Study registry were genotyped for two GCLC promoter polymorphisms; the GCLC -129 C to T single nucleotide polymorphism (GCLC -129 SNP) and the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR). Glutamate decarboxylase antibody (GAD65Ab) positive T1D patients with the GCLC -129 SNP C/T genotype have increased GAD65Ab levels (p-value, <0.05) compared to the GCLC -129 SNP C/C genotype. T1D patients with an age-at-onset of 14-35 years who possess the GCLC -129 SNP T/T genotype have a higher GAD65Ab index than T1D patients with the GCLC -129 SNP C/C genotype (p-value <0.05). In addition, T1D patients with an age-at-onset of 14-35 years possess the GCLC TNR 7/8 genotype at a lower frequency than the control subjects (OR, 0.33, 95% CI, 0.13-0.82). The GCLC -129 SNP and GCLC TNR appear to be in linkage disequilibrium (p-value<0.0001). These results suggest that GCLC promoter polymorphisms may influence GAD65Ab levels and may influence the age at which T1D is diagnosed.

Key words

type 1 diabetes - GCLC - promoter polymorphisms - glutathione

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Correspondence

L. M. Bekris

Department of Medicine

University of Washington

Box 358280

Seattle

WA 98195

Phone: +206/277/64 55

Fax: +206/543/31 69

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