Certain mutations within the interleukin 2 receptor alpha (IL2RA) gene region are associated with juvenile idiopathic arthritis (JIA), according to a team of scientists
“The IL2RA gene has previously been shown to be associated with type 1 diabetes, Graves' disease, rheumatoid arthritis, and multiple sclerosis and so may be linked with a predisposition to autoimmunity in general,” remarks Wendy Thomson, Ph.D., of the University of Manchester, U.K. who led the study. “Our results have shown that the genetic variants of the IL2RA gene are strongly associated with JIA in two independent cohorts.”
The researchers specifically studied SNPs rs2104286, rs41295061, and rs11594656. They report that rs2104286 was significantly associated with U.K. cases of JIA. The association was strongest in a cohort of patients with oligoarthritis, the most common subtype of JIA. This SNP was most strongly linked with female patients and those positive for antinuclear antibodies (ANA). A second SNP rs41295061, one of two SNPs previously associated with type 1 diabetes, also showed modest evidence for association with JIA, according to the investigators.
This association with rs2104286 was replicated in a second study cohort of JIA cases from the U.S. The analysis yielded highly significant evidence for association, the researchers state.
The U.K. cohort consisted of 654 JIA cases and 3,849 controls. Genotype data for SNP rs2104286 for controls was combined with the data for that SNP obtained from a genome-wide association study (WTCCC GWA), giving a total control sample size of 6,787. Genotyping was performed using the Sequenom iPlex platform. Association analysis was performed using PLINK, a genome-data analysis toolset.
Groups were stratified according to the commonly accepted seven categories of JIA (called ILAR subgroups), ANA antibody status, and gender. Data for rs2104286 was also available, from a GWA study of 747 Caucasian North American JIA cases and 1,161 controls.
The results of this study were presented at “EULAR 2008”, the annual congress of the European League Against Rheumatism held in Paris.