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)

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.

References

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