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 Chayama & 2 others Yusuke Nakamura, Koichi Matsuda

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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

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Genome-Wide Association Study
Major Histocompatibility Complex
Hepacivirus
Liver Cirrhosis
Chronic Hepatitis C
Population
Single Nucleotide Polymorphism
Biomarkers
Alleles
Odds Ratio
Chromosomes
Logistic Models
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Urabe, Yuji ; Ochi, Hidenori ; Kato, Naoya ; Kumar, Vinod ; Takahashi, Atsushi ; Muroyama, Ryosuke ; Hosono, Naoya ; Otsuka, Motoyuki ; Tateishi, Ryosuke ; Lo, Paulisally Hau Yi ; Tanikawa, Chizu ; Omata, Masao ; Koike, Kazuhiko ; Miki, Daiki ; Abe, Hiromi ; Kamatani, Naoyuki ; Toyota, Joji ; Kumada, Hiromitsu ; Kubo, Michiaki ; Chayama, Kazuaki ; Nakamura, Yusuke ; Matsuda, Koichi. / A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region. In: Journal of Hepatology. 2013 ; Vol. 58, No. 5. pp. 875-882.
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title = "A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region",
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.",
author = "Yuji Urabe and Hidenori Ochi and Naoya Kato and Vinod Kumar and Atsushi Takahashi and Ryosuke Muroyama and Naoya Hosono and Motoyuki Otsuka and Ryosuke Tateishi and Lo, {Paulisally Hau Yi} and Chizu Tanikawa and Masao Omata and Kazuhiko Koike and Daiki Miki and Hiromi Abe and Naoyuki Kamatani and Joji Toyota and Hiromitsu Kumada and Michiaki Kubo and Kazuaki Chayama and Yusuke Nakamura and Koichi Matsuda",
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Urabe, Y, Ochi, H, Kato, N, Kumar, V, Takahashi, A, Muroyama, R, Hosono, N, Otsuka, M, Tateishi, R, Lo, PHY, Tanikawa, C, Omata, M, Koike, K, Miki, D, Abe, H, Kamatani, N, Toyota, J, Kumada, H, Kubo, M, Chayama, K, Nakamura, Y & 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, vol. 58, no. 5, pp. 875-882. https://doi.org/10.1016/j.jhep.2012.12.024

A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region. / Urabe, Yuji; Ochi, Hidenori; Kato, Naoya; Kumar, Vinod; Takahashi, Atsushi; Muroyama, Ryosuke; Hosono, Naoya; Otsuka, Motoyuki; Tateishi, Ryosuke; Lo, Paulisally Hau Yi; Tanikawa, Chizu; Omata, Masao; Koike, Kazuhiko; Miki, Daiki; Abe, Hiromi; Kamatani, Naoyuki; Toyota, Joji; Kumada, Hiromitsu; Kubo, Michiaki; Chayama, Kazuaki; Nakamura, Yusuke; Matsuda, Koichi.

In: Journal of Hepatology, Vol. 58, No. 5, 01.05.2013, p. 875-882.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region

AU - Urabe, Yuji

AU - Ochi, Hidenori

AU - Kato, Naoya

AU - Kumar, Vinod

AU - Takahashi, Atsushi

AU - Muroyama, Ryosuke

AU - Hosono, Naoya

AU - Otsuka, Motoyuki

AU - Tateishi, Ryosuke

AU - Lo, Paulisally Hau Yi

AU - Tanikawa, Chizu

AU - Omata, Masao

AU - Koike, Kazuhiko

AU - Miki, Daiki

AU - Abe, Hiromi

AU - Kamatani, Naoyuki

AU - Toyota, Joji

AU - Kumada, Hiromitsu

AU - Kubo, Michiaki

AU - Chayama, Kazuaki

AU - Nakamura, Yusuke

AU - Matsuda, Koichi

PY - 2013/5/1

Y1 - 2013/5/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.jhep.2012.12.024

DO - 10.1016/j.jhep.2012.12.024

M3 - Article

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JO - Journal of Hepatology

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