4cba6e0d-a435-456e-831d-0f75ae7c46b1
title
Evidence for  CTLA4  as a susceptibility gene for systemic lupus erythematosus.
eb098d44-2653-41e8-9fb9-1ad5afe6927e
abstract
Several lines of evidence implicate the  Cytotoxic T Lymphocyte Antigen 4  ( CTLA4 ) gene in susceptibility to autoimmune disease. We have examined the association of systemic lupus erythematosus (SLE) with polymorhisms within the  CTLA4  gene that were previously proposed to regulate  CTLA-4  function: a  single nucleotide polymorphism (SNP) in position +49 of exon 1  and a dinucleotide repeat in the 3' untranslated region (3'UTR). The 3'UTR repeat showed a significant association with SLE, with one allele conferring susceptibility and another conferring protection to the disease. The associated alleles do not support previous suggestions of an allele size-dependent effect of the 3' UTR polymorphism in autoimmunity development and instead suggest that it is in linkage disequilibrium with a true causative locus. No association of the exon 1 SNP with SLE was found in our population. Given the conflicting results obtained in different studies on the association of SLE with this polymorphism, we performed a meta-analysis including seven previously published studies and the present one. Significantly increased and decreased risks for SLE were found for carriers of the G allele and the A allele, respectively. The functional characterization of disease-associated  CTLA4  gene variants is now required to elucidate their role in the pathogenesis of SLE and other autoimmune diseases.