Association of SLC22A4/5 Polymorphisms with Steroid Responsiveness of Inflammatory Bowel Disease in Japan

Purpose: We investigated the association between steroid responsiveness and single nucleotide polymorphisms ofSLC22A4/A5located within inflammatory bowel disease 5 locus. Our goal is personalized steroid therapy adjusted to match individual variations in drug responsiveness in each inflammatory bowel disease patient. Methods: Unrelated Japanese cohorts of 94 patients with Crohn's, 94 patients with ulcerative colitis, and 257 healthy control subjects were consecutively enrolled in this study. Genotyping and haplotype analysis focusing on steroid responsiveness was performed by using 15 single nucleotide polymorphisms. Results: The G allele of −368T > G inSLC22A5, in which strong linkage disequilibrium was observed and the limited diversity of three haplotypes was estimated, was significantly associated with steroid resistance in Japanese patients with Crohn's disease (P= 0.016). Haplotype analysis between −446C > T and −368T > G in theSLC22A5promoter region showed that the CG allele appeared to be a risk haplotype for steroid resistance (CG: odds ratio, 4.13; 95 percent confidence interval, 1.41-12.1;P= 0.016). Conclusions: This extensive linkage disequilibrium may form a general risk haplotype for steroid resistance in Crohn's disease in Japanese. Further analyses of the pharmacogenomics of steroid responsiveness are warranted to achieve the goal of individualized steroid therapy against inflammatory bowel disease.