Genome-wide association study of high-sensitivity C-reactive protein, D-dimer, and interleukin-6 levels in multiethnic HIV+ cohorts.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
02 02 2021
02 02 2021
Historique:
pubmed:
24
10
2020
medline:
7
4
2021
entrez:
23
10
2020
Statut:
ppublish
Résumé
Elevated levels of interleukin-6 (IL-6), D-dimer, and C-reactive protein (hsCRP) are associated with increased incidence of comorbid disease and mortality among people living with HIV (PLWH). Prior studies suggest a genetic basis for these biomarker elevations in the general population. The study objectives are to identify the genetic basis for these biomarkers among PLWH. Baseline levels of hsCRP, D-dimer, and IL-6, and single nucleotide polymorphisms (SNPs) were determined for 7768 participants in three HIV treatment trials. Single variant analysis was performed for each biomarker on samples from each of three ethnic groups [African (AFR), Admixed American (AMR), European (EUR)] within each trial including covariates relevant to biomarker levels. For each ethnic group, the results were pooled across trials, then further pooled across ethnicities. The transethnic analysis identified three, two, and one known loci associated with hsCRP, D-dimer, and IL-6 levels, respectively, and two novel loci, FGB and GCNT1, associated with D-dimer levels. Lead SNPs exhibited similar effects across ethnicities. Additionally, three novel, ethnic-specific loci were identified: CATSPERG associated with D-dimer in AFR and PROX1-AS1 and TRAPPC9 associated with IL-6 in AFR and AMR, respectively. Eleven loci associated with three biomarker levels were identified in PLWH from the three studies including six loci known in the general population and five novel loci associated with D-dimer and IL-6 levels. These findings support the hypothesis that host genetics may partially contribute to chronic inflammation in PLWH and help to identify potential targets for intervention of serious non-AIDS complications.
Identifiants
pubmed: 33095540
pii: 00002030-202102020-00003
doi: 10.1097/QAD.0000000000002738
pmc: PMC7789909
mid: NIHMS1647964
doi:
Substances chimiques
Biomarkers
0
Fibrin Fibrinogen Degradation Products
0
Interleukin-6
0
fibrin fragment D
0
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
193-204Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI120197
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AI999999
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI046957
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI046362
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068641
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL129956
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI136780
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI042170
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.
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