Association of TNFSF15 polymorphisms in Korean children with Crohn's disease.

Abstract

Genome-wide association studies have identified tumor necrosis factor superfamily member 15 (TNFSF15) as a Crohn's disease (CD)-related gene. The aim of this study was to evaluate the association between five TNFSF15 polymorphisms and CD in Korean children and analyze their genotypes in relation to phenotype. Five single-nucleotide polymorphisms of TNFSF15 (rs3810936, rs6478108, rs6478109, rs7848647, rs7865494) were genotyped in 108 CD patients and in 599 healthy controls. Risk allele, genotype, and haplotype were analyzed in CD patients and controls, and genotype-phenotype relationships were studied. There were significant associations of rs3810936, rs6478108, rs6478109, rs7848647 with CD in Korean pediatric patients (P = 6.5×10(-8), P = 1.3×10(-8), P = 3.7×10(-8), P = 2.9×10(-8), respectively). The adjusted OR (aOR) for the homozygous risk allele genotype was significantly higher than that for the homozygous genotype for the opposite allele: rs3810936, aOR, 5.36 (95%CI: 2.61-10.98, P = 4.6×10(-6)); rs6478108, aOR, 6.62 (95%CI: 3.03-14.46, P = 2.2×10(-6)); rs6478109, aOR, 6.24 (95%CI: 2.85-13.66, P = 4.6×10(-6)); rs7848647, aOR, 6.32 (95%CI: 2.89-13.81, P = 3.8×10(-6)). The risk allele of rs3810936 was associated with later symptom onset, later diagnosis, and the presence of perianal lesion (P = 0.013, P = 0.016 and P = 0.029). There was a significant association of TNFSF15 with pediatric CD in Korean patients.