Association study of <i><scp>MICA</scp></i> gene polymorphisms with rheumatoid arthritis susceptibility in south Tunisian population

Summary The aim of this study was to investigate the role of major histocompatibility complex ( MHC ) class I chain‐related gene A ( MICA ) polymorphisms, important in natural killer ( NK ) cell function, in patients with rheumatoid arthritis ( RA ). A transmembrane ( TM ) alanine‐encoding GCT repeats, termed A4, A5, A5.1, A6 and A9 in the MICA gene, and single‐nucleotide polymorphisms ( SNP s): the Met129Val polymorphism (rs1051792) and the nonsynonymously coding SNP (rs1051794) were genotyped in 142 patients with RA and 123 unrelated healthy individuals using, respectively, PCR fluorescent method, nested PCR ‐ RFLP and allele specific PCR ( ASP ). Association was assessed based on the χ 2 test, genotype relative risk ( GRR ) and odds ratio ( OR ) with 95% confidence intervals ( CI s). Our results show a trend of association of the different MICA genotypes G/G, G/A and A/A ( P  = 0.029) which did not attain the significance after Bonferroni's correction ( p c  = 0.08). Although, we revealed a significant association of the genotype A/A of MICA ‐250 in patients with RA compared to healthy controls ( pc  = 0.033). In contrast, no significant differences between alleles and genotypes frequencies were found either with MICA ‐ TM or MICA met129 val ( P  >   0.05) in our sample. Moreover, stratification of patients with RA according to clinical and immunological data for the different polymorphisms studied shows a significant association of both MICA ‐250 G allele ( pc  = 0.0075) and MICA ‐250 GG genotype ( pc  = 0.008) and both allelic (val) ( pc  = 0.021) and genotypic (val/val) distribution ( p c  = 0.0095) for MICA met129 val in the RF ‐positive subgroup compared to RF ‐negative patients with RA . In contrast, we found a strong association of the MICA ‐ TM A9 allele in RF ‐negative patients with RA ( p c  = 0.0003). This study indicates the involvement of the MICA ‐250 polymorphism in the genetic susceptibility and severity to RA and suggests that variations in MICA ‐ TM and MICA met129 val may have an effect on RA severity in our south Tunisian sample.