TY - JOUR
T1 - Replicated association of 17q12-21 with susceptibility of primary biliary cirrhosis in a Japanese cohort
AU - Tanaka, Atsushi
AU - Invernizzi, P.
AU - Ohira, H.
AU - Kikuchi, K.
AU - Nezu, S.
AU - Kosoy, R.
AU - Seldin, Michael F
AU - Gershwin, M. Eric
AU - Takikawa, H.
PY - 2011/7
Y1 - 2011/7
N2 - 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, Pc = 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.
AB - 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, Pc = 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.
KW - Autoimmune disease
KW - Genetic polymorphism
KW - Single nucleotide polymorphism
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U2 - 10.1111/j.1399-0039.2011.01684.x
DO - 10.1111/j.1399-0039.2011.01684.x
M3 - Article
C2 - 21506939
AN - SCOPUS:79958769177
VL - 78
SP - 65
EP - 68
JO - HLA
JF - HLA
SN - 2059-2302
IS - 1
ER -