The CTLA4 + 49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland

Abstract

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation.We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods.The +49 A allele was increased in RA (61.2%; P = 0.02; OR = 1.28; 95% C.I. = 1.04 -1.58) and JIA (61.8%; P = 0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls ( P value < 0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively).Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population. D

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

“…15 SNPs within the CTLA4 gene, previously associated with T1D and autoimmune thyroid disease 17 have previously been examined in JIA with conflicting results. 22,23 This may reflect true genetic heterogeneity at this locus or may be due to the modest sample sizes used in previous investigations. We found a weak association of the CTLA4 CT60 SNP (rs3087243) with UK JIA cases (Table 1), although this study only had 53% power to detect an effect (Supplementary Table 2).…”

Emerging patterns of risk factor make‐up enable subclassification of rheumatoid arthritis

“…Because CTLA4 polymorphisms have been associated with several immune diseases, CTLA4 seems to be a general susceptibility locus for autoimmunity, most likely through an altered ability to dampen T cell responses. The association between the A49G single-nucleotide polymorphism in CTLA4 and RA has been frequently investigated, but the results have been inconsistent (39). More recently, however, it was suggested that CTLA4 confers risk to only the subset of ACPA-positive RA patients and not to patients with ACPA-negative disease, potentially adding a third genetic risk factor that contributes mainly to ACPApositive disease (40).…”

Polymorphisms in the CTLA-4 Gene and Rheumatoid Arthritis Susceptibility: A Meta-analysis

“…It inhibits T cell activation and maintains peripheral tolerance. As T cells play major roles in the pathogenesis of RA, therefore, regulators of T cells may be influenced by disease susceptibility, such as CTLA-4 [4,12,15,[19][20][21]. The CTLA-4 gene is located on chromosome 2q33 and encodes a 223 amino acid protein [22].…”