Replicated association of 17q12-21 with susceptibility of primary biliary cirrhosis in a Japanese cohort

Tissue Antigens. 2011 Jul;78(1):65-8. doi: 10.1111/j.1399-0039.2011.01684.x. Epub 2011 Apr 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics*
  • Chromosomes, Human, Pair 17 / genetics*
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interleukin-12 Subunit p35 / genetics
  • Liver Cirrhosis, Biliary / ethnology
  • Liver Cirrhosis, Biliary / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Interleukin-12 / genetics
  • beta Karyopherins / genetics

Substances

  • IL12A protein, human
  • IL12RB2 protein, human
  • IRF5 protein, human
  • Interferon Regulatory Factors
  • Interleukin-12 Subunit p35
  • Receptors, Interleukin-12
  • TNPO3 protein, human
  • beta Karyopherins