title: Lack of association between IBD5 and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease.
abstract: OBJECTIVE
  Population-specific differences in the genetic susceptibility to inflammatory bowel disease (IBD) are indicated by the fact that Crohn's disease (CD) in Japanese patients does not have any of the common CARD15 variants that are associated with CD in Caucasians. Recently, the disease-causing mutation in the IBD5 haplotype was identified. The TC haplotype, composed of L503F in SLC22A4 and -207G/C in SLC22A5 promoters, was reported to alter the function of the organic cation transporter and to be associated with CD in Caucasians. To determine whether the TC haplotype is also associated with IBD in a Japanese population, we genotyped L503F and -207G/C variants in Japanese subjects. Furthermore, we also performed a case-control association study with all representative single nucleotide polymorphisms (SNPs) in IBD5 using previous information of linkage disequilibrium extension reported in Japanese patients to determine whether there were variants in IBD5 specifically associated with IBD in Japanese patients.
  
  
  METHODS
  A total of 758 Japanese individuals, 241 patients with CD, 247 patients with ulcerative colitis (UC) and 270 healthy controls, were analyzed in this study. Genotyping for SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis.
  
  
  RESULTS
  We found L503F and -207G/C to be very rare (<1% frequency) in CD, UC and HC in the Japanese population. Furthermore, we also found that none of the representative SNPs in IBD5 was associated with CD or UC in the Japanese subjects.
  
  
  CONCLUSIONS
  In contrast to Caucasians, IBD5 is not a major component of the susceptibility to IBD in the Japanese population.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. mtosa@int3.med.tohoku.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Tosa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Negoro
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kinouchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Abe
authors.forename: Eiki
authors.initials: E
authors.lastname: Nomura
authors.forename: Sho
authors.initials: S
authors.lastname: Takagi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aihara
authors.forename: Shinya
authors.initials: S
authors.lastname: Oomori
authors.forename: Mikako
authors.initials: M
authors.lastname: Sugimura
authors.forename: Kazuma
authors.initials: K
authors.lastname: Takahashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hiwatashi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D002895:Chromosomes, Human, Pair 5; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007564:Japan; D008297:Male; D053473:Nod2 Signaling Adaptor Protein; D020641:Polymorphism, Single Nucleotide
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein