CTLA-4 polymorphism at position 49 in exon 1 and susceptibility to type 1 autoimmune hepatitis

CTLA-4 expressed on activated T cells, binds to B7 molecules and functions as a negative regulator of T cell activation. In theory, reduced expression or function of CTLA-4 might augment autoimmunity. Recently an A-G polymorphism in exon 1 of the CTLA-4 gene was associated with predisposition to AIH type1 (AIH-1) and several other autoimmune diseases in white individuals in distinct populations. We investigated the frequency of this polymorphism in Iranian patients with AIH-1, using a case-control association analysis.

Peripheral blood mononuclear cells’ DNA were prepared from AIH patients (n=76) and healthy controls (n=185). Determination of CTLA-4 genotypes was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method.

The allele frequency for G allele was 25.6% and 24.3% in patients and healthy controls, respectively that shows no significant difference in subjects with AIH as compared to the healthy controls. Meanwhile, the frequencies of AA, AG and GG genotypes in patients and in healthy controls revealed no statistical difference in the distribution of CTLA-4 genotype in the studied groups.

This study demonstrates that susceptibility to AIH in Iranian population is not influenced by exon 1 CTLA-4 gene polymorphisms at position 49. This polymorphism may either have a recent founder population or be associated with AIH only among the Caucasians.