A functionally relevant IRF5 haplotype is associated with reduced risk to Wegener's granulomatosis

Stefan Wieczorek*, Julia U. Holle, Stephanie Müller, Harald Fricke, Wolfgang L. Gross, Jörg T. Epplen

*Korrespondierende/r Autor/-in für diese Arbeit
19 Zitate (Scopus)


Wegener's granulomatosis (WG), characterized by systemic vasculitis and granulomatous inflammation, is a rare chronic rheumatic condition potentially sharing some etiopathological principles with other autoimmune disorders, e.g., rheumatoid arthritis (RA) and systemic lupus erythomatosus (SLE). Several large association studies have identified genetic risk factors for RA and SLE. Thereof, we have evaluated the relevance of the most promising ones in WG. 22 single nucleotide polymorphisms (SNPs) within or in the vicinity of CCL21, CD40, CDK6, IL21, IL2RB, IRF5, KIF5A, KLF12, MMEL1, PRKCQ, STAT4, TNFAIP3, and TRAF1/C5 have been genotyped in >600 German WG cases and >800 matched controls. While most polymorphisms did not show suspicious effects on WG susceptibility, SNPs representing TNFAIP3 (rs6922466, p∈=∈0.032, odds ratio (OR) 0.83, 95% confidence interval (CI) 0.7 - 0.98) and CDK6 (rs42041, p∈=∈0.0201, OR 1.21, 95% CI 1.03-1.43) revealed nominally significant differences in allele distribution. The strongest association was detected for a functionally relevant four SNP haplotype of IRF5, which comprised a protective effect (p∈=∈0.0000897, p corrected∈=∈0.0012, OR 0.73, 95% CI 0.62-0.85) similar to those previously seen in RA and SLE. Thus, we suggest that WG, SLE, and RA share some, but not many, genetic risk factors, which supports models of partly overlapping etiopathogical mechanisms in these disorders.
ZeitschriftJournal of Molecular Medicine
Seiten (von - bis)413-421
PublikationsstatusVeröffentlicht - 01.04.2010


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