A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE

作者：Sandling Johanna K; Garnier Sophie; Sigurdsson Snaevar; Wang Chuan; Nordmark Gunnel; Gunnarsson Iva; Svenungsson Elisabet; Padyukov Leonid; Sturfelt Gunnar; Jonsen Andreas; Bengtsson Anders A; Truedsson Lennart; Eriksson Catharina; Rantapaa Dahlqvist Solbritt; Malarstig Anders; Strawbridge Rona J; Hamsten Anders; Criswell Lindsey A; Graham Robert R; Behrens Timothy W; Eloranta Maija Leena; Alm Gunnar; Ronnblom Lars; Syvanen Ann Christine^*

来源：European Journal of Human Genetics, 2011, 19(4): 479-484.

DOI：10.1038/ejhg.2010.197

• systemic lupus erythematosus
• type I interferon system
• candidate gene study
• single nucleotide polymorphism
• IKBKE
• IL8

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 2010

• 出版日期2011-4