title: Association study of MICA gene polymorphisms with rheumatoid arthritis susceptibility in south Tunisian population.
abstract: 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 (SNPs): 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 χ2 test, genotype relative risk (GRR) and odds ratio (OR) with 95% confidence intervals (CIs). 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 (pc = 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 (pc = 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 (pc = 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.
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia.
authors.forename: Y
authors.initials: Y
authors.lastname: Achour
authors.forename: A
authors.initials: A
authors.lastname: Kammoun
authors.forename: M
authors.initials: M
authors.lastname: Ben Hamad
authors.forename: N
authors.initials: N
authors.lastname: Mahfoudh
authors.forename: S
authors.initials: S
authors.lastname: Chaabane
authors.forename: S
authors.initials: S
authors.lastname: Marzouk
authors.forename: L
authors.initials: L
authors.lastname: Keskes
authors.forename: L
authors.initials: L
authors.lastname: Gaddour
authors.forename: Z
authors.initials: Z
authors.lastname: Bahloul
authors.forename: A
authors.initials: A
authors.lastname: Maalej
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014416:Tunisia
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A