Article Text

Download PDFPDF
Role of the MHC2TA gene in autoimmune diseases
  1. Alfonso Martínez1,
  2. Marta Sánchez-Lopez2,
  3. Jezabel Varadé1,
  4. Ana Mas1,
  5. M Carmen Martín1,
  6. Virginia de las Heras3,
  7. Rafael Arroyo3,
  8. Juan Luis Mendoza4,
  9. Manuel Díaz-Rubio4,
  10. Benjamín Fernández-Gutiérrez2,
  11. Emilio G de la Concha1,
  12. Elena Urcelay1
  1. 1Immunology Department, Hospital Universitario San Carlos, Madrid, Spain
  2. 2Rheumatology Department, Hospital Universitario San Carlos, Madrid, Spain
  3. 3Neurology Department, Hospital Universitario San Carlos, Madrid, Spain
  4. 4Gastroenterology Department, Hospital Universitario San Carlos, Madrid, Spain
  1. Correspondence to:
    Dr E Urcelay
    Immunology Department, Hospital Universitario San Carlos, Martin Lagos s/n, 28040 Madrid, Spain; eurcelay.hcsc{at}


Objectives: 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.

Aim: 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.

  • CIITA, class II transactivator
  • HLA, human leucocyte antigen
  • IBD, inflammatory bowel disease
  • MHC, major histocompatibility complex

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published Online First 29 September 2006

  • Competing interests: None.