A single nucleotide polymorphism in exon 1 of cytotoxic T-lymphocyte-associated-4 (CTLA-4) is not associated with rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is an oligogenic disease for which only one susceptibility locus has been identified to date. Genes involved in T-cell regulation are potential candidates. Association to cytotoxic T-lymphocyte-associated-4 (CTLA-4) protein, a negative regulator of T-cell activation, has previously been described in a subset of German RA patients carrying the HLA DRB1*0401 subtype. Linkage and association with another oligogenic autoimmune disease, insulin-dependent diabetes mellitus, has also been described in a Spanish population. Objective. To investigate the association of CTLA-4 with RA in Spanish and UK subjects. Methods. Caucasoid UK RA patients (n = 192), UK controls (n = 96), Spanish RA patients (n = 136) and Spanish controls (n = 144) were typed for an A/G bi-allelic polymorphism in exon 1 of CTLA-4 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) (enzyme). Results. No significant differences in the frequency of the G allele or the GG genotype were found in either the UK or Spanish RA patients compared with controls. Conclusion. No significant evidence was found of an association between RA and CTLA-4.