A genome‐wide association study on low susceptibility to hepatitis C virus infection (GEHEP012 study)
- 17 June 2019
- journal article
- research article
- Published by Wiley in Liver International
- Vol. 39 (10), 1918-1926
- https://doi.org/10.1111/liv.14177
Abstract
Background A low proportion of individuals repeatedly exposed to the hepatitis C virus (HCV) remain uninfected. This condition could have a genetic basis but it is not known whether or not it is mainly driven by a high-penetrance common allele. Objective To explore whether low susceptibility to HCV infection is mainly driven by a high-penetrance common allele. Methods In this genome-wide association study (GWAS), a total of 804 HCV-seropositive individuals and 27 high-risk HCV-seronegative (HRSN) subjects were included. Plink and Magma software were used to carry out single nucleotide polymorphism (SNP)-based and gene-based association analyses respectively. Results No SNP nor any gene was associated with low susceptibility to HCV infection after multiple testing correction. However, SNPs previously associated with this trait and allocated within the LDLR gene, rs5925 and rs688, were also associated with this condition in our study under a dominant model (24 out of 27 [88.9%] rs5925-C carriers in the HRSN group vs 560 of 804 [69.6%] rs5925-C carriers in the HCV-seropositive group, P = 0.031, odds ratio [OR] = 3.48; 95% confidence interval [CI] = 1.04-11.58; and 24 out of 27 [88.9%] rs688-T carriers in the HRSN group vs 556 of 804 [69.1%] rs688-T carriers in the HCV-seropositive group, P = 0.028, OR = 3.57, 95% CI = 1.65-11.96). Conclusions Low susceptibility to HCV infection does not seem to be mainly driven by a high-penetrant common allele. By contrast, it seems a multifactorial trait where genes such as LDLR could be involved.Funding Information
- Ministerio de Ciencia e Innovación (CP18/00111, CP18/00146)
- Instituto de Salud Carlos III (I3SNS, PI13/02434, PI16/01861, RD12/0017/0012, RD16/0025/0040)
- Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (B-0037, C-0009-2015, PI-0001/2017)
This publication has 24 references indexed in Scilit:
- A host cell RNA-binding protein, Staufen1, has a role in hepatitis C virus replication before virus assemblyJournal of General Virology, 2013
- CD81 sequence and susceptibility to hepatitis C infectionJournal of Medical Virology, 2013
- Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 ControlsPLoS Pathogens, 2013
- Affinity Capture and Identification of Host Cell Factors Associated with Hepatitis C Virus (+) Strand Subgenomic RNAMolecular & Cellular Proteomics, 2013
- Hepatocytes That Express Variants of Cyclophilin A Are Resistant to HCV Infection and ReplicationGastroenterology, 2012
- Guidelines for Genome-Wide Association StudiesPLoS Genetics, 2012
- Meta-Regression of Hepatitis C Virus Infection in Relation to Time Since Onset of Illicit Drug Injection: The Influence of Time and PlaceAmerican Journal of Epidemiology, 2008
- Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infectionClinical and Experimental Immunology, 2008
- Association of genetic polymorphism of low‐density lipoprotein receptor with chronic viral hepatitis C infection in Han ChineseJournal of Medical Virology, 2006
- EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cellsBiochemical Journal, 2003