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

Nordmark, G.; Kristjansdottir, G.; Theander, Elke LU ; Eriksson, P.; Brun, J. G.; Wang, C.; Padyukov, L.; Truedsson, Lennart LU ; Alm, G. and Eloranta, M-L, et al. (2009) In Genes and Immunity 10(1). p.68-76
Abstract
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... (More)
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. (Less)
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published
subject
keywords
insertion-deletion polymorphism, IRF5, primary Sjogren's syndrome, single nucleotide, STAT4, polymorphisms
in
Genes and Immunity
volume
10
issue
1
pages
68 - 76
publisher
Nature Publishing Group
external identifiers
  • wos:000262580600010
  • scopus:59149104204
ISSN
1476-5470
DOI
10.1038/gene.2008.94
language
English
LU publication?
yes
id
449a4f62-34c0-4c59-ac33-5ace0af02f11 (old id 1312638)
date added to LUP
2009-03-18 08:57:20
date last changed
2017-10-22 03:45:03
@article{449a4f62-34c0-4c59-ac33-5ace0af02f11,
  abstract     = {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) &gt; 1.4 and P-values &lt; 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.},
  author       = {Nordmark, G. and Kristjansdottir, G. and Theander, Elke and Eriksson, P. and Brun, J. G. and Wang, C. and Padyukov, L. and Truedsson, Lennart and Alm, G. and Eloranta, M-L and Jonsson, R. and Ronnblom, L. and Syvanen, A-C},
  issn         = {1476-5470},
  keyword      = {insertion-deletion polymorphism,IRF5,primary Sjogren's syndrome,single nucleotide,STAT4,polymorphisms},
  language     = {eng},
  number       = {1},
  pages        = {68--76},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjogren's syndrome},
  url          = {http://dx.doi.org/10.1038/gene.2008.94},
  volume       = {10},
  year         = {2009},
}