title: Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus.
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.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Barreto
authors.forename: Eugénia
authors.initials: E
authors.lastname: Santos
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ferreira
authors.forename: Constantin
authors.initials: C
authors.lastname: Fesel
authors.forename: Maria Francisca
authors.initials: MF
authors.lastname: Fontes
authors.forename: Clara
authors.initials: C
authors.lastname: Pereira
authors.forename: Berta
authors.initials: B
authors.lastname: Martins
authors.forename: Rita
authors.initials: R
authors.lastname: Andreia
authors.forename: João Faro
authors.initials: JF
authors.lastname: Viana
authors.forename: Francisco
authors.initials: F
authors.lastname: Crespo
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferreira
authors.forename: Astrid Moura
authors.initials: AM
authors.lastname: Vicente
mesh_terms: D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D017931:DNA Primers; D018900:Dinucleotide Repeats / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011174:Portugal; D015183:Restriction Mapping
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D017931:DNA Primers