Research article - Peer-reviewed, 2011
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A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE
Sandling, Johanna K.; Garnier, Sophie; Sigurdsson, Snaevar; Wang, Chuan; Nordmark, Gunnel; Gunnarsson, Iva; Svenungsson, Elisabet; Padyukov, Leonid; Sturfelt, Gunnar; Jönsen, Andreas; Bengtsson, Anders A; Truedsson, Lennart; Eriksson, Catharina; Rantapää-Dahlqvist, Solbritt; Mälarstig, Anders; Strawbridge, Rona J; Hamsten, Anders; Criswell, Lindsey A; Graham, Robert R; Behrens, Timothy W; Eloranta, Maija-Leena; Alm, Gunnar; Rönnblom, Lars; Syvänen, Ann-ChristineShow less authors
Abstract
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P < 0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P(meta)=3.3 x 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis. European Journal of Human Genetics (2011) 19, 479-484; doi:10.1038/ejhg.2010.197; published online 22 December 2010Keywords
systemic lupus erythematosus; type I interferon system; candidate gene study; single nucleotide polymorphism; IKBKE; IL8Published in
European Journal of Human Genetics2011, volume: 19, number: 4, pages: 479-484
Publisher: NATURE PUBLISHING GROUP
Authors' information
Sandling, Johanna K.
Uppsala University
Garnier, Sophie
Uppsala University
Sigurdsson, Snaevar
Uppsala University
Wang, Chuan
Uppsala University
Nordmark, Gunnel
Uppsala University
Gunnarsson, Iva
Karolinska Institute
Svenungsson, Elisabet
Karolinska Institute
Padyukov, Leonid
Karolinska Institute
Sturfelt, Gunnar
Lund University
Jönsen, Andreas
Lund University
Bengtsson, Anders A
Truedsson, Lennart
Lund University
Eriksson, Catharina
Umeå University Hospital (NUS)
Rantapää-Dahlqvist, Solbritt
Umeå University Hospital (NUS)
Mälarstig, Anders
Karolinska Institute
Strawbridge, Rona J
Karolinska Institute
Hamsten, Anders
Karolinska Institute
Criswell, Lindsey A
University of California
Graham, Robert R
Genentech Inc.
Behrens, Timothy W
Genentech Inc.
Eloranta, Maija-Leena
Uppsala University
Alm, Gunnar
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Rönnblom, Lars
Uppsala University
Syvänen, Ann-Christine
Uppsala University
UKÄ Subject classification
Biochemistry and Molecular Biology
Genetics
Publication Identifiers
DOI: https://doi.org/10.1038/ejhg.2010.197
URI (permanent link to this page)
https://res.slu.se/id/publ/47068