Objectives: A recent genomewide association study from a Japanese population identified tumor necrosis factor superfamily member 15 (TNFSF15) as an inflammatory bowel disease gene. Previous studies have shown that expression of TNFSF15 was upregulated in macrophages and lymphocytes of the intestinal lamina propria of Crohn's disease (CD) patients. Here, we have tested four single nucleotide polymorphisms (SNPs) of TNFSF15 in Korean patients to determine whether the gene is associated with susceptibility to CD in a closely related population.
Methods: Four SNPs across TNFSF15 were genotyped in 380 patients with CD and 380 healthy controls.
Results: Carriers of three polymorphisms, including rs3810936, rs6478108, and rs7848647, showed statistically significant association with CD (adjusted OR [aOR] 2.81, 95% confidence interval [CI] 1.94-4.07, P= 4.4 x 10(-8); aOR 3.49, 95% CI 2.42-5.04, P= 2.7 x 10(-11); and aOR 3.49, 95% CI 2.42-5.03, P= 2.2 x 10(-11), respectively). Following haplotype analysis, homozygotes carrying two copies of the haplotype consisting of the risk alleles of those three SNPs showed statistically significant association with CD (aOR 5.39, 95% CI 3.19-9.10, P= 3.07 x 10(-10)).
Conclusions: Our data support the hypothesis that the TNFSF15 genotypes play an important role in the pathogenesis of CD in Koreans.