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Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus

Sigurdsson, S; Nordmark, G; Goring, HHH; Lindroos, K; Wiman, AC; Sturfelt, Gunnar LU ; Jönsen, Andreas LU ; Rantapaa-Dahlqvist, S; Moller, B and Kere, J, et al. (2005) In American Journal of Human Genetics 76(3). p.528-537
Abstract
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms ( SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control... (More)
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms ( SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes - the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes - we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P < 10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system. (Less)
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published
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American Journal of Human Genetics
volume
76
issue
3
pages
528 - 537
publisher
Cell Press
external identifiers
  • wos:000226851900016
  • pmid:15657875
  • scopus:13844292408
ISSN
0002-9297
DOI
10.1086/428480
language
English
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yes
id
bbd57dbc-d70e-4445-a900-fc006f818c5e (old id 253952)
date added to LUP
2007-08-22 16:23:21
date last changed
2017-11-19 03:25:47
@article{bbd57dbc-d70e-4445-a900-fc006f818c5e,
  abstract     = {Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms ( SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes - the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes - we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P &lt; 10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system.},
  author       = {Sigurdsson, S and Nordmark, G and Goring, HHH and Lindroos, K and Wiman, AC and Sturfelt, Gunnar and Jönsen, Andreas and Rantapaa-Dahlqvist, S and Moller, B and Kere, J and Koskenmies, S and Widen, E and Eloranta, ML and Julkunen, H and Kristjansdottir, H and Steinsson, K and Alm, G and Ronnblom, L and Syvanen, AC},
  issn         = {0002-9297},
  language     = {eng},
  number       = {3},
  pages        = {528--537},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1086/428480},
  volume       = {76},
  year         = {2005},
}