Association of signal transducer and activator of transcription 4 genetic variants with extra-intestinal manifestations in inflammatory bowel disease.

Aims: The STAT4 gene encodes a transcription factor which plays an important role in the development of inflammation of many immune-mediated diseases. We investigated the relationship between STAT4 single nucleotide polymorphisms (SNPs) and susceptibility to ulcerative colitis (UC) and Crohn's disease (CD) and disease phenotypes in the Korean population.

Main Methods: We performed a case-control association study in individuals with UC (N=246), CD (N=182), and healthy controls (N=229).

Key Findings: We genotyped 8 STAT4 SNPs (rs11889341, rs7574865, rs8179673, rs6752770, rs925847, rs10168266, rs10181656, and rs11685878) in the STAT4 gene in patients and controls. SNP rs925847 in the STAT4 gene was significantly associated with susceptibility to UC (P=0.025; OR=0.63) in dominant genotype analysis, though none of these SNPs were associated with CD susceptibility. Moreover, a significant association was identified between SNP rs11889341 and joint involvement (P=0.040; OR=3.79), and between SNP rs925847 and eye involvement (P=0.030; OR=2.42) in UC patients. For CD, rs925847 genetic variant was associated with joint (P=0.029; OR=3.93) and perianal lesions (P=0.033; OR=2.27).

Significance: Our data demonstrated that the STAT4 genetic variants could predispose an individual to IBD and its extra-intestinal ailments in Koreans, suggesting the common pathogenesis of IBD (especially, extra-intestinal manifestations) and other autoimmune diseases.