Contribution of susceptibility variants at FCGR2A and 13q12 to the risk of relapse among Japanese patients with ulcerative colitis.

Abstract

Recent genome-wide association studies have identified nearly 100 susceptibility genes for ulcerative colitis (UC). However, the contribution of susceptibility variants for UC to clinical outcome has scarcely been reported. The aim of this study was to investigate whether UC-associated genetic variants confer a risk of clinical relapse. One hundred and nine consecutive Japanese subjects with quiescent UC were recruited. Four genetic variants of HLA-DRB1*1502, rs6671847 at FCGR2A, rs17085007 at 13q12, and rs2108225 at SLC26A3 were genotyped by Invader assay. The clinical courses were followed after blood sampling, and the risk of relapse according to these genotypes was calculated by Cox proportional hazard model. During the mean follow-up period of 35 months (range 1-81 months), 49 of 109 subjects (45 %) relapsed. Carriers of the G allele of rs6671847 showed an increased risk of relapse compared with non-carriers [adjusted hazard ratio (HR), 2.27; 95 % confidence interval (CI), 1.20-4.32; p = 0.01]. Patients with the CT or TT genotypes of rs17085007 also had an increased risk of relapse compared to subjects with the CC genotype (for CT: adjusted HR, 2.16; 95 % CI, 1.10-4.23; p = 0.03; for TT: adjusted HR, 3.25; 95 % CI, 1.18-8.95; p = 0.02). These two risk variants multiplied the risk of relapse by 2.74 times (95 % CI, 1.10-4.23; p = 0.01) in patients with one risk genotype and 5.40 times (95 % CI, 2.06-14.13; p = 0.0006) in patients with both risk genotypes. Genetic variants of rs6671847 at FCGR2A and rs17085007 at 13q12 conferred a risk of relapse in patients with UC.