Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset

Publication

Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset

Journal Paper/Review - Apr 29, 2010

Glas Jürgen, Roeske Darina, Müller-Myhsok Bertram, Diegelmann Julia, Ochsenkühn Thomas, Göke Burkhard, Folwaczny Matthias, Lohse Peter, Epplen Jörg T, Klein Wolfram, Pfennig Simone, Weidinger Maria, Beigel Florian, Fries Christoph, Nagy Melinda, Seiderer Julia, Brand Stephan

Citation

Glas J, Roeske D, Müller-Myhsok B, Diegelmann J, Ochsenkühn T, Göke B, Folwaczny M, Lohse P, Epplen J, Klein W, Pfennig S, Weidinger M, Beigel F, Fries C, Nagy M, Seiderer J, Brand S. Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset. PloS one 2010; 5:e10373.

Type

Journal Paper/Review (English)

Journal

PloS one 2010; 5

Publication Date

Apr 29, 2010

Issn Electronic

1932-6203

Pages

e10373

Brief description/objective

BACKGROUND
Recent studies demonstrated an association of STAT4 variants with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), indicating that multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 variants on the susceptibility and phenotype of inflammatory bowel diseases (IBD) in a large patient and control cohort.

METHODOLOGY/PRINCIPAL FINDINGS
Genomic DNA from 2704 individuals of Caucasian origin including 857 patients with Crohn's disease (CD), 464 patients with ulcerative colitis (UC), and 1383 healthy, unrelated controls was analyzed for seven SNPs in the STAT4 gene (rs11889341, rs7574865, rs7568275, rs8179673, rs10181656, rs7582694, rs10174238). In addition, a detailed genotype-phenotype analysis was performed. Our analysis revealed an association of the STAT4 SNP rs7574865 with overall decreased susceptibility to CD (p = 0.047, OR 0.86 [95% CI 0.74-0.99]). However, compared to CD patients carrying the wild type genotype, the STAT4 SNP rs7574865 was significantly associated with early CD onset (p = 0.021) and colonic CD (p = 0.008; OR = 4.60, 95% CI 1.63-12.96). For two other STAT4 variants, there was a trend towards protection against CD susceptibility (rs7568275, p = 0.058, OR 0.86 [95% CI 0.74-1.00]; rs10174238, p = 0.057, OR 0.86 [95% CI 0.75-1.00]). In contrast, we did not observe any association with UC susceptibility. Evidence for weak gene-gene interaction of STAT4 with the IL23R SNP rs11209026 was lost after Bonferroni correction.

CONCLUSIONS/SIGNIFICANCE
Our results identified the STAT4 SNP rs7574865 as a disease-modifying gene variant in colonic CD. However, in contrast to SLE and RA, the effect of rs7574865 on CD susceptibility is only weak.