@article{f09c1690717e44bf8e2430e03ca3ed51,
title = "SNP rs688 within the low-density lipoprotein receptor (LDL-R) gene associates with HCV susceptibility",
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.",
keywords = "HCV, HIV-1, LDL-R, polymorphism, rs688, single nucleotide",
author = "GS Steba and Koekkoek, \{Sylvie M.\} and Tanck, \{Michael W.T.\} and Vanhommerig, \{Joost W.\} and \{van der Meer\}, \{Jan T.M.\} and David Kwa and Kees Brinkman and Maria Prins and Ben Berkhout and Georgios Pollakis and Richard Molenkamp and Janke Schinkel and Paxton, \{William A.\}",
note = "Funding Information: Funding information The research leading to these results has received funding from the European Community's Seventh Framework Programme [FP7-2007-2013] under grant agreement no. HEALTH-F3-2012-305578. We would like to thank all ACS and MOSAIC participants as well as Margreet Bakker and Astrid Newsum for cohort management support. This work was conducted within the framework of the Amsterdam Cohort Studies on HIV infection and AIDS (Website: www.amsterdamcohortstudies.org), a collaboration between the Public Health Service of Amsterdam, the Academic Medical Center of the University of Amsterdam, Sanquin Blood Supply Foundation, the University Medical Center Utrecht and the Dutch HIV Monitoring Foundation. The MOSAIC cohort was supported by the {"}AIDS Fonds{"}(grant numbers 2008 026 and 2013 037) and funding was provided from the European Community's Seventh Framework Programme [FP7-2007-2013] under grant agreement no. HEALTH-F3-2012-305578. Funding Information: We would like to thank all ACS and MOSAIC participants as well as Margreet Bakker and Astrid Newsum for cohort management support. This work was conducted within the framework of the Amsterdam Cohort Studies on HIV infection and AIDS (Website: www.amsterdamcohortstudies.org), a collaboration between the Public Health Service of Amsterdam, the Academic Medical Center of the University of Amsterdam, Sanquin Blood Supply Foundation, the University Medical Center Utrecht and the Dutch HIV Monitoring Foundation. The MOSAIC cohort was supported by the {"}AIDS Fonds{"}(grant numbers 2008 026 and 2013 037) and funding was provided from the European Community{\textquoteright}s Seventh Framework Programme [FP7‐2007‐2013] under grant agreement no. HEALTH‐F3‐2012‐305578. Publisher Copyright: {\textcopyright} 2018 The Authors. Liver International Published by John Wiley \& Sons Ltd",
year = "2019",
month = mar,
doi = "10.1111/liv.13978",
language = "English",
volume = "39",
pages = "463--469",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",
}