Steba, Gaby S, Koekkoek, Sylvie M, Tanck, Michael WT, Vanhommerig, Joost W, van der Meer, Jan TM, Kwa, David, Brinkman, Kees, Prins, Maria, Berkhout, Ben, Pollakis, Georgios 
ORCID: 0000-0002-9659-5461 et al (show 4 more authors)
(2019)
SNP rs688 within the low-density lipoprotein receptor (LDL-R) gene associates with HCV susceptibility.
Liver International, 39 (3).
pp. 463-469.
Abstract
BACKGROUND & AIMS: Despite high-risk behaviour, 10%-20% of HCV multiple exposed individuals remain uninfected (MEU), whilst the remainder become infected (MEI). We hypothesize that host factors play a role in HCV susceptibility. We aimed to identify polymorphisms in host genes that encode for proteins involved in viral entry: CD81, Scavenger receptor 1 (SR-1), Low-density lipoprotein receptor (LDL-R), Claudin-1 (CLDN1), Occludin (OCLN) and Niemann-Pick C1-like 1 (NPC1L1). METHODS:Multiple exposed infected and MEU from two observational cohorts were selected. From the MSM study of acute infection with HCV (MOSAIC), HIV-1 infected MEU cases (n = 30) and HIV-1 infected MEI controls (n = 32) were selected based on reported high-risk behaviour. From the Amsterdam Cohorts Studies (ACS) injecting drug users (IDU) cohort, MEU cases (n = 40) and MEI controls (n = 22) were selected who injected drugs for ≥2 years, in the nineties, when HCV incidence was high. Selected single nucleotide polymorphisms (SNPs) were determined by sequencing or SNP assays. RESULTS:No associations were found for SNPs within genes coding for CD81, SR-1, Claudin-1 or Occludin between the MEU and MEI individuals from either cohort. We did observe a significant association for rs688 within the LDL-R gene with HCV infection (OR: 0.41 P = 0.001), however, LDL cholesterol levels did not vary between individuals carrying the differential SNPs. Additionally, a marginal significant effect was found for rs217434 and rs2072183 (OR: 2.07 P = 0.032 and OR: 1.76 P = 0.039, respectively) within NPC1L1. CONCLUSIONS:Our results demonstrate that the rs688 SNP within the LDL-R gene associates with HCV susceptibility through mucosal as well as intravenous exposure.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HCV, HIV-1, LDL-R, polymorphism, rs688, single nucleotide |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 14 Feb 2019 10:53 |
| Last Modified: | 19 Jan 2023 01:05 |
| DOI: | 10.1111/liv.13978 |
| Open Access URL: | http://doi.org/10.1111/liv.13978 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3032026 |
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