title: Role of the MHC2TA gene in autoimmune diseases.
abstract: OBJECTIVE
  Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (-168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction in a northern European population. However, no evidence of association of this MHC2TA variant with the two autoimmune diseases could be subsequently detected in independent cohorts.
  
  
  OBJECTIVE
  To test the aforementioned single nucleotide polymorphism and another G-->C change (nt1614 from coding sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene.
  
  
  METHODS
  A case-control study was performed with 350 patients with rheumatoid arthritis, 396 patients with multiple sclerosis, 663 patients with inflammatory bowel disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by using TaqMan assays-on-demand on a 7900HT analyser, following the manufacturer's suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were inferred with the expectation-maximisation algorithm implemented by the Arlequin software.
  
  
  RESULTS
  No independent association with these autoimmune diseases was found for either polymorphism in the Spanish cohorts tested. However, when haplotypes were compared between patients with rheumatoid arthritis and controls, a significant difference in their overall frequency distribution was observed, evidencing a protective haplotype (-168A/1614C, p = 0.006; odds ratio (OR) 0.7) and a risk haplotype (-168G/1614C, p = 0.019; OR 1.6). Patients with multiple sclerosis mirrored these results, but no effect on IBD was identified.
  
  
  CONCLUSIONS
  The MHC2TA gene influences predisposition to rheumatoid arthritis and multiple sclerosis, but not to IBD. The -168G allele is not an aetiological variant in itself, but a genetic marker of susceptibility/protection haplotypes.
authors.affiliation: Immunology Department, Hospital Universitario San Carlos, Martin Lagos s/n, 28040 Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
authors.forename: Marta
authors.initials: M
authors.lastname: Sánchez-Lopez
authors.forename: Jezabel
authors.initials: J
authors.lastname: Varadé
authors.forename: Ana
authors.initials: A
authors.lastname: Mas
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Martín
authors.forename: Virginia
authors.initials: V
authors.lastname: de Las Heras
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Mendoza
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio
authors.forename: Benjamín
authors.initials: B
authors.lastname: Fernández-Gutiérrez
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015534:Trans-Activators / Q000235:genetics*
chemical_list: C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators