CTLA4 CT60 gene polymorphism is not associated with differential susceptibility to pemphigus foliaceus

Márcia Regina Pincerati,Ricardo Dalla-Costa,Maria Luiza Petzl-Erler

doi:10.1590/s1415-47572010005000073

Márcia Regina Pincerati, Ricardo Dalla-Costa + Show 1 more

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https://doi.org/10.1590/s1415-47572010005000073

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Abstract

Pemphigus foliaceus is an organ-specific autoimmune disease characterized by autoantibodies against the extracellular region of desmoglein 1, a protein that mediates intercellular adhesion in desmosomes. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key negative regulator of the T cell immune response, playing an important role in T cell homeostasis and maintenance of peripheral tolerance. Polymorphisms in the CTLA4 gene have been associated with autoimmune diseases and the functional CT60 single nucleotide polymorphism (rs3087243, also named 6230G > A) has been proposed to be a casual variant in several of these diseases. The aim of this study was to ascertain whether this polymorphism is associated with inter-individual variation in susceptibility to pemphigus foliaceus. The population sample in this case-control association study comprised 248 patient and 367 controls. We did not found a significant association of pemphigus foliaceus with the CT60 variants. We conclude that the CTLA4CT60 polymorphism is not an important factor for pemphigus foliaceus pathogenesis in the population analyzed.

Highlights

The 2q33 chromosome region harbors genes that encode costimulatory molecules, such as the cytotoxic T-lymphocyte-associated protein 4 (CTLA4), the cluster of differentiation molecule 28 (CD28) and the inducible costimulatory molecule (ICOS), all of which play crucial roles in T cell activation and regulation (Ling et al, 2001)
Recent studies suggested that polymorphisms in the CTLA4 gene may influence the development of autoimmune diseases
Endemic pemphigus foliaceus (PF), known as fogo selvagem, is an organ-specific autoimmune disease characterized by autoantibodies against desmoglein 1 protein and by loss of adhesion between keratinocytes, leading to intraepithelial blisters of the skin (Warren et al, 2000)

Summary

Introduction

The 2q33 chromosome region harbors genes that encode costimulatory molecules, such as the cytotoxic T-lymphocyte-associated protein 4 (CTLA4), the cluster of differentiation molecule 28 (CD28) and the inducible costimulatory molecule (ICOS), all of which play crucial roles in T cell activation and regulation (Ling et al, 2001). Polymorphisms in CTLA4 are associated with a very wide range of inflammatory and autoimmune diseases (for a review, see Kristiansen et al, 2000; Gough et al, 2005). The authors found associations between polymorphisms in the segment that includes the 3’ region of the CTLA4 gene with

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