Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset.

Abstract:

:Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction involving auto-reactive T-cells, pro-inflammatory cytokines, reactive oxygen species (ROS) and loss of insulin. Monozygotic twin studies show a 20-60% concordance with T1D indicating there may be an environmental component to the disease. Glutathione (GSH) is the major endogenous antioxidant produced by the cell. GSH participates directly in the neutralization of free radicals and plays a role in the immune response. Glutathione-s-transferases (GSTs) conjugate GSH to free-radicals or xenobiotics. GST activity depletes GSH levels and may either detoxify or enhance the toxicity of a compound. Glutathione-s-transferase mu 1 (GSTM1) and glutathione-s-transferase theta 1 (GSTT1) have polymorphic homozygous deletion (null) genotypes resulting in complete absence of enzyme activity. GSTM1 and GSTT1 null genotypes in Caucasian populations have frequencies of approximately 40-60% and 15-20%, respectively. GST null genotypes have been associated with susceptibility to cancer and protection against chronic pancreatitis. The aim of this study was to investigate associations with GSTM1 and GSTT1 polymorphisms in a group T1D patients and control subjects 0-35 years old who participated in the Combined Swedish Childhood Diabetes Registry and Diabetes Incidence Study (1986-1988). Results show that the presence of the GSTM1 and not the null genotype (OR, 2.13 95% CI, 1.23-3.70, p-value, 0.007, Bonferroni corrected p-value, 0.035) may be a susceptibility factor in T1D 14-20 years old. These results suggest that the GSTM1 null genotype is associated with T1D protection and T1D age-at-onset and that susceptibility to T1D may involve GST conjugation.

journal_name

Autoimmunity

journal_title

Autoimmunity

authors

Bekris LM,Shephard C,Peterson M,Hoehna J,Van Yserloo B,Rutledge E,Farin F,Kavanagh TJ,Lernmark A

doi

10.1080/08916930500407238

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

567-75

issue

8

eissn

0891-6934

issn

1607-842X

pii

PL22464056J43641

journal_volume

38

pub_type

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