A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region
Autor: | Ryosuke Muroyama, Yuji Urabe, Paulisally Hau Yi Lo, Yusuke Nakamura, Kazuaki Chayama, Naoyuki Kamatani, Naoya Hosono, Michiaki Kubo, Hiromi Abe, Chizu Tanikawa, Daiki Miki, Vinod Kumar, Masao Omata, Ryosuke Tateishi, Motoyuki Otsuka, Atsushi Takahashi, Hiromitsu Kumada, Hidenori Ochi, Joji Toyota, Naoya Kato, Koichi Matsuda, Kazuhiko Koike |
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Rok vydání: | 2012 |
Předmět: |
Adult
Liver Cirrhosis Male Genotype Hepatitis C virus Single-nucleotide polymorphism Genome-wide association study Hepacivirus Biology medicine.disease_cause Polymorphism Single Nucleotide HLA-DQ alpha-Chains Major Histocompatibility Complex Primary biliary cirrhosis Asian People Japan Risk Factors medicine Humans Genetic Predisposition to Disease Genetic Testing Allele Alleles Aged Hepatology Case-control study Odds ratio Hepatitis C Middle Aged medicine.disease Genetic Loci Case-Control Studies Immunology Female Genome-Wide Association Study HLA-DRB1 Chains |
Zdroj: | Journal of hepatology. 58(5) |
ISSN: | 1600-0641 |
Popis: | 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 −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 ( p combined =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. |
Databáze: | OpenAIRE |
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