title: Association of SLC22A4/5 polymorphisms with steroid responsiveness of inflammatory bowel disease in Japan.
abstract: OBJECTIVE
  We investigated the association between steroid responsiveness and single nucleotide polymorphisms of SLC22A4/A5 located 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 in SLC22A5, 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 the SLC22A5 promoter 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.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Nakahara
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Arimura
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Saito
authors.forename: Akira
authors.initials: A
authors.lastname: Goto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Motoya
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D001499:Bayes Theorem; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074058:Solute Carrier Family 22 Member 5; D013256:Steroids / Q000627:therapeutic use*; D027981:Symporters
chemical_list: D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D013256:Steroids; D027981:Symporters