Association of SLC22A4/5 polymorphisms with steroid responsiveness of inflammatory bowel disease in Japan.
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.
Nakahara
Seiya
S
First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
Arimura
Yoshiaki
Y
Saito
Katsuhiko
K
Goto
Akira
A
Motoya
Satoshi
S
Shinomura
Yasuhisa
Y
Miyamoto
Atsushi
A
Imai
Kohzoh
K
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
D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D013256:Steroids; D027981:Symporters