RGD Reference Report - A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region. - Rat Genome Database

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

Authors: 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 
Citation: Urabe Y, etal., J Hepatol. 2013 May;58(5):875-82. doi: 10.1016/j.jhep.2012.12.024. Epub 2013 Jan 12.
RGD ID: 14401563
Pubmed: PMID:23321320   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jhep.2012.12.024   (Journal Full-text)


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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver cirrhosis susceptibilityISOHLA-DQA1 (Homo sapiens)14401563; 14401563associated with Hepatitis C more ...RGD 
liver cirrhosis susceptibilityIAGP 14401563associated with Hepatitis C more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Ba  (RT1 class II, locus Ba)

Genes (Mus musculus)
H2-Aa  (histocompatibility 2, class II antigen A, alpha)

Genes (Homo sapiens)
HLA-DQA1  (major histocompatibility complex, class II, DQ alpha 1)


Additional Information