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CTLA-4 gene polymorphism confers susceptibility to primary biliary cirrhosis.

Abstract：

BACKGROUND/AIM:Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease thought to develop through a complex interaction of genetic and environmental factors. It is characterised by T-cell-mediated non-suppurative destructive cholangitis. We have studied the polymorphic cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene, which encodes a molecule that is a vital negative regulator of T-cell activation, as a candidate susceptibility locus for PBC. This gene on chromosome 2q33 (designated IDDM12) is associated with susceptibility to both type 1 diabetes and autoimmune thyroid disease. METHODS:The CTLA-4 exon 1 polymorphism (A/G encoding for threonine or alanine, respectively) was genotyped via polymerase chain reaction in 200 Caucasoid PBC patients and 200 non-related geographically matched Caucasoid controls. RESULTS:There was significant overrepresentation of the G/A and G/G genotypes in PBC patients compared to controls (G/A 53% vs 40%; G/G 18.5% vs 10.5%, Odds Ratio (OR)=2.45 [95% CI 1.6-3.7], p=0.00006, chi2=19.4). Likewise, there was a significant difference in allele frequencies (G encoding alanine at codon 17, PBC 0.45 vs controls 0.305: OR=1.9 [1.4-2.5], p<0.0002). This association remained significant (p=0.00027) when patients with autoimmune thyroid disease were excluded from the analysis. CONCLUSIONS:The CTLA-4 exon 1 polymorphism is the first non-major histocompatibility complex gene to be identified as a susceptibility locus for PBC. Our data support the hypothesis that clinically distinct autoimmune disease may be controlled by a common set of susceptibility genes.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Agarwal K,Jones DE,Daly AK,James OF,Vaidya B,Pearce S,Bassendine MF

doi

10.1016/s0168-8278(00)80213-5

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

538-41

issue

4

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(00)80213-5

journal_volume

32

pub_type

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