title: Replicated association of 17q12-21 with susceptibility of primary biliary cirrhosis in a Japanese cohort.
abstract: To examine the genetics of susceptibility to primary biliary cirrhosis (PBC), genome-wide association studies GWAS have been performed in patients of European ancestry and have shown the significant associations of IL12-related pathways, SPIB, IRF5-TNPO3, and 17q12-21. We tested whether these findings could be extended to a Japanese cohort, 303 Japanese PBC and 298 controls. We failed to detect significant associations at IL12A (rs574808, rs1075498) and IL12RB2 (rs3790567). There was no genetic variance at IRF5-TNPO3 (rs10488631) in Japanese. A single nucleotide polymorphism (SNP) at SPIB (rs3745516) reached nominal significance, but the corrected P value did not reach significance. For the 17q12-21 region, two SNPs had nominally significant associations [GSDMB (rs2305480, P = 0.022) and ZPBP2 (rs11557467, P = 0.021)] and we noted a significant P value at a SNP in IKZF3 (rs939327, P = 0.0024, P(c) = 0.017) after correction for multiple comparisons. Thus, these results indicate a haplotype on 17q12-21 with a similar association in Japanese and European PBC.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. a-tanaka@med.teikyo-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: P
authors.initials: P
authors.lastname: Invernizzi
authors.forename: H
authors.initials: H
authors.lastname: Ohira
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: S
authors.initials: S
authors.lastname: Nezu
authors.forename: R
authors.initials: R
authors.lastname: Kosoy
authors.forename: M F
authors.initials: MF
authors.lastname: Seldin
authors.forename: M E
authors.initials: ME
authors.lastname: Gershwin
authors.forename: H
authors.initials: H
authors.lastname: Takikawa
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D053765:Interleukin-12 Subunit p35 / Q000235:genetics; D008105:Liver Cirrhosis, Biliary / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053707:Receptors, Interleukin-12 / Q000235:genetics; D028961:beta Karyopherins / Q000235:genetics
chemical_list: C508858:IL12A protein, human; C508439:IL12RB2 protein, human; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D053765:Interleukin-12 Subunit p35; D053707:Receptors, Interleukin-12; C546476:TNPO3 protein, human; D028961:beta Karyopherins