A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region

Yuji Urabe, Hidenori Ochi, Naoya Kato, Vinod Kumar, Atsushi Takahashi, Ryosuke Muroyama, Naoya Hosono, Motoyuki Otsuka, Ryosuke Tateishi, Paulisally Hau Yi Lo, Chizu Tanikawa, Masao Omata, Kazuhiko Koike, Daiki Miki, Hiromi Abe, Naoyuki Kamatani, Joji Toyota, Hiromitsu Kumada, Michiaki Kubo, Kazuaki ChayamaYusuke Nakamura, Koichi Matsuda

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47 Citations (Scopus)

Abstract

Background & Aims: We performed a genome-wide association study (GWAS) of hepatitis C virus (HCV)-induced liver cirrhosis (LC) to identify predictive biomarkers for the risk of LC in patients with chronic hepatitis C (CHC). Methods: A total of 682 HCV-induced LC cases and 1045 CHC patients of Japanese origin were genotyped by Illumina Human Hap 610-Quad bead Chip. Results: Eight SNPs which showed possible associations (p <1.0 × 10-5) at the GWAS stage were further genotyped using 936 LC cases and 3809 CHC patients. We found that two SNPs within the major histocompatibility complex (MHC) region on chromosome 6p21, rs910049 and rs3135363, were significantly associated with the progression from CHC to LC (pcombined = 9.15 × 10 -11 and 1.45 × 10-10, odds ratio (OR) = 1.46 and 1.37, respectively). We also found that HLA-DQA1*0601 and HLA-DRB1*0405 were associated with the progression from CHC to LC (p = 4.53 × 10-4 and 1.54 × 10-4 with OR = 2.80 and 1.45, respectively). Multiple logistic regression analysis revealed that rs3135363, rs910049, and HLA-DQA1*0601 were independently associated with the risk of HCV-induced LC. In addition, individuals with four or more risk alleles for these three loci have a 2.83-fold higher risk for LC than those with no risk allele, indicating the cumulative effects of these variations. Conclusions: Our findings elucidated the crucial roles of multiple genetic variations within the MHC region as prognostic/predictive biomarkers for CHC patients.

Original languageEnglish
Pages (from-to)875-882
Number of pages8
JournalJournal of Hepatology
Volume58
Issue number5
DOIs
Publication statusPublished - 01-05-2013

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Urabe, Y., Ochi, H., Kato, N., Kumar, V., Takahashi, A., Muroyama, R., Hosono, N., Otsuka, M., Tateishi, R., Lo, P. H. Y., Tanikawa, C., Omata, M., Koike, K., Miki, D., Abe, H., Kamatani, N., Toyota, J., Kumada, H., Kubo, M., ... Matsuda, K. (2013). A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region. Journal of Hepatology, 58(5), 875-882. https://doi.org/10.1016/j.jhep.2012.12.024