title: A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region.
abstract: OBJECTIVE
  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.
authors: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Yuji
authors: Y
authors: Urabe
authors: Hidenori
authors: H
authors: Ochi
authors: Naoya
authors: N
authors: Kato
authors: Vinod
authors: V
authors: Kumar
authors: Atsushi
authors: A
authors: Takahashi
authors: Ryosuke
authors: R
authors: Muroyama
authors: Naoya
authors: N
authors: Hosono
authors: Motoyuki
authors: M
authors: Otsuka
authors: Ryosuke
authors: R
authors: Tateishi
authors: Paulisally Hau Yi
authors: PH
authors: Lo
authors: Chizu
authors: C
authors: Tanikawa
authors: Masao
authors: M
authors: Omata
authors: Kazuhiko
authors: K
authors: Koike
authors: Daiki
authors: D
authors: Miki
authors: Hiromi
authors: H
authors: Abe
authors: Naoyuki
authors: N
authors: Kamatani
authors: Joji
authors: J
authors: Toyota
authors: Hiromitsu
authors: H
authors: Kumada
authors: Michiaki
authors: M
authors: Kubo
authors: Kazuaki
authors: K
authors: Chayama
authors: Yusuke
authors: Y
authors: Nakamura
authors: Koichi
authors: K
authors: Matsuda
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D005838:Genotype; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007564:Japan; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D059811:HLA-DRB1 Chains; C493960:HLA-DRB1*04:05 antigen