Glutamate cysteine ligase catalytic subunit promoter polymorphisms and associations with type 1 diabetes age-at-onset and GAD65 autoantibody levels

Exp Clin Endocrinol Diabetes. 2007 Apr;115(4):221-8. doi: 10.1055/s-2007-970574.

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.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoantibodies / blood*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Genotype
  • Glutamate Decarboxylase / immunology*
  • Glutamate-Cysteine Ligase / genetics*
  • Humans
  • Infant
  • Isoenzymes / immunology*
  • Male
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*

Substances

  • Autoantibodies
  • Isoenzymes
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2
  • Glutamate-Cysteine Ligase