SNP rs688 within the low-density lipoprotein receptor (LDL-R) gene associates with HCV susceptibility.
Adult
Female
Genetic Predisposition to Disease
Hepacivirus
/ pathogenicity
Hepatitis C
/ epidemiology
Host-Pathogen Interactions
Humans
Incidence
Male
Middle Aged
Netherlands
/ epidemiology
Polymorphism, Single Nucleotide
Receptors, LDL
/ genetics
Risk Factors
Sexual Behavior
Sexually Transmitted Diseases, Viral
/ epidemiology
Substance Abuse, Intravenous
/ complications
HCV
HIV-1
LDL-R
polymorphism
rs688
single nucleotide
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
27
03
2018
revised:
17
09
2018
accepted:
19
09
2018
pubmed:
28
9
2018
medline:
14
4
2020
entrez:
28
9
2018
Statut:
ppublish
Résumé
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). 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. 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. Our results demonstrate that the rs688 SNP within the LDL-R gene associates with HCV susceptibility through mucosal as well as intravenous exposure.
Sections du résumé
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.
Identifiants
pubmed: 30260075
doi: 10.1111/liv.13978
pmc: PMC6588020
doi:
Substances chimiques
LDLR protein, human
0
Receptors, LDL
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
463-469Informations de copyright
© 2018 The Authors. Liver International Published by John Wiley & Sons Ltd.
Références
Med J Aust. 2013 Mar 4;198(4):210-4
pubmed: 23451966
PLoS One. 2011;6(12):e29322
pubmed: 22216248
BMC Infect Dis. 2006 Jun 08;6:93
pubmed: 16762050
J Infect Dis. 2018 Jan 17;217(3):353-357
pubmed: 29140443
Euro Surveill. 2017 May 25;22(21):
pubmed: 28597832
Medicine (Baltimore). 1995 Jul;74(4):212-20
pubmed: 7623656
Nature. 2010 Aug 5;466(7307):707-13
pubmed: 20686565
PLoS Pathog. 2016 May 06;12(5):e1005610
pubmed: 27152966
Hepatology. 2002 Nov;36(5 Suppl 1):S99-105
pubmed: 12407582
Nat Med. 2012 Jan 08;18(2):281-5
pubmed: 22231557
J Hum Genet. 1998;43(3):153-9
pubmed: 9747026
Nat Genet. 2009 Oct;41(10):1100-4
pubmed: 19749758
Nature. 2009 Sep 17;461(7262):399-401
pubmed: 19684573
Atherosclerosis. 2010 Nov;213(1):200-5
pubmed: 20832063
Liver Int. 2019 Mar;39(3):463-469
pubmed: 30260075
Hum Mol Genet. 2013 Apr 1;22(7):1424-31
pubmed: 23297366
Hum Mol Genet. 2007 Jul 15;16(14):1765-72
pubmed: 17517690
J Hepatol. 1998 Aug;29(2):207-13
pubmed: 9722201
Am J Epidemiol. 2008 Nov 15;168(10):1099-109
pubmed: 18849303
J Infect Dis. 2001 Jul 1;184(1):16-21
pubmed: 11398104
Open Forum Infect Dis. 2015 Aug 06;2(3):ofv115
pubmed: 26634219
AIDS. 1988 Feb;2(1):55-60
pubmed: 3128998
PLoS One. 2011 Mar 08;6(3):e17781
pubmed: 21408083
J Hepatol. 2007 Mar;46(3):411-9
pubmed: 17156886
World J Gastroenterol. 2007 May 7;13(17):2436-41
pubmed: 17552026
Am J Epidemiol. 1987 Jun;125(6):1048-57
pubmed: 3495173
Clin Infect Dis. 2013 May;56(10):1480-7
pubmed: 23386630