Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis

Objective Juvenile idiopathic arthritis (JIA) is an autoimmune disorder mediated by Th1 immune responses. CTLA‐4, expressed on the T cell surface, plays a negative role in regulating T cell activation. Single‐nucleotide polymorphisms (SNPs) in CTLA4 have been implicated in susceptibility to several autoimmune disorders, including JIA. This study was undertaken to test 3 functional CTLA4 variants for association with JIA. Methods Families of 531 children with JIA were genotyped for SNPs located in the promoter region (C−318T), exon 1 (A49G), and the 3′‐untranslated region (CT60) of CTLA4 by polymerase chain reaction amplification and digestion. Family Based Association Testing (FBAT) was used to test CTLA4 SNPs and haplotypes for association with JIA. A second independent cohort of >300 children with JIA and >500 controls were genotyped for case–control analyses. Case–control analyses of the combined cohorts, as well as meta‐analyses of published association studies of CTLA4 and JIA, were performed. Results There were no deviations of transmission of any of the CTLA4 variants to children with JIA, or JIA subtypes, determined by FBAT. No significant associations between CTLA4 C−318T or A49G SNPs and JIA were found in 650 JIA cases and 350 controls. Similarly, no significant associations with CT60 variants were found in >800 JIA cases and >500 controls. The meta‐analysis also failed to confirm an association between JIA and CTLA4 variants. Conclusion These results suggest that C−318T, A49G, CT60, and haplotypes tagged by these CTLA4 SNPs are not associated with JIA or major JIA subtypes.