Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA- 4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA- 4 gene in RA have provided conflicting results. In order to determine association of the CTLA- 4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA- 4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA- 4 +49 and CT60 in RA patients differed significantly from controls (P = 0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (x(2) = 10.58, d.f. = 3, P = 0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4+49 G allele was associated with the risk of RA. These results suggested that the CTLA- 4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.