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Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjogren's syndrome

In English

Författare

  • G. Nordmark
  • G. Kristjansdottir
  • Elke Theander
  • P. Eriksson
  • J. G. Brun
  • C. Wang
  • L. Padyukov
  • Lennart Truedsson
  • G. Alm
  • M-L Eloranta
  • R. Jonsson
  • L. Ronnblom
  • A-C Syvanen
Visa allt

Summary, in English

Primary Sjogren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) > 1.4 and P-values < 0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P = 2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.

Publiceringsår

2009

Språk

Engelska

Sidor

68-76

Publikation/Tidskrift/Serie

Genes and Immunity

Volym

10

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Nature Publishing Group

Ämne

  • Immunology in the medical area

Nyckelord

  • insertion-deletion polymorphism
  • IRF5
  • primary Sjogren's syndrome
  • single nucleotide
  • STAT4
  • polymorphisms

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1476-5470