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Comparative genetic analyses point to HCP5 as susceptibility locus for HCV-associated hepatocellular carcinoma

Lange, C. M. and Bibert, S. and Dufour, J. F. and Cellerai, C. and Cerny, A. and Heim, M. H. and Kaiser, L. and Malinverni, R. and Mullhaupt, B. and Negro, F. and Semela, D. and Moradpour, D. and Kutalik, Z. and Bochud, P. Y.. (2013) Comparative genetic analyses point to HCP5 as susceptibility locus for HCV-associated hepatocellular carcinoma. Journal of hepatology, Vol. 59, H. 3. pp. 504-509.

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Official URL: http://edoc.unibas.ch/dok/A6338536

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Abstract

BACKGROUND & AIMS: Recently, genetic variations in MICA (lead single nucleotide polymorphism [SNP] rs2596542) were identified by a genome-wide association study (GWAS) to be associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in Japanese patients. In the present study, we sought to determine whether this SNP is predictive of HCC development in the Caucasian population as well. METHODS: An extended region around rs2596542 was genotyped in 1924 HCV-infected patients from the Swiss Hepatitis C Cohort Study (SCCS). Pair-wise correlation between key SNPs was calculated both in the Japanese and European populations (HapMap3: CEU and JPT). RESULTS: To our surprise, the minor allele A of rs2596542 in proximity of MICA appeared to have a protective impact on HCC development in Caucasians, which represents an inverse association as compared to the one observed in the Japanese population. Detailed fine-mapping analyses revealed a new SNP in HCP5 (rs2244546) upstream of MICA as strong predictor of HCV-related HCC in the SCCS (univariable p=0.027; multivariable p=0.0002, odds ratio=3.96, 95% confidence interval=1.90-8.27). This newly identified SNP had a similarly directed effect on HCC in both Caucasian and Japanese populations, suggesting that rs2244546 may better tag a putative true variant than the originally identified SNPs. CONCLUSIONS: Our data confirms the MICA/HCP5 region as susceptibility locus for HCV-related HCC and identifies rs2244546 in HCP5 as a novel tagging SNP. In addition, our data exemplify the need for conducting meta-analyses of cohorts of different ethnicities in order to fine map GWAS signals.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0168-8278
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:14
Deposited On:10 Apr 2015 09:14

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