The Role of Global and Local Ancestry on Clopidogrel Response in African Americans.
Journal
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
ISSN: 2335-6936
Titre abrégé: Pac Symp Biocomput
Pays: United States
ID NLM: 9711271
Informations de publication
Date de publication:
2023
2023
Historique:
entrez:
21
12
2022
pubmed:
22
12
2022
medline:
23
12
2022
Statut:
ppublish
Résumé
Pharmacogenomics has long lacked dedicated studies in African Americans, resulting in a lack of indepth data in this populations. The ACCOuNT consortium has collected a cohort of 167 African American patients on steady state clopidogrel with the goal of discovering population specific variation that may contribute to the response of this anti-platelet agent. Here we analyze the role of both global and local ancestry on the clinical phenotypes of P2Y12 reaction units (PRU) and high on-treatment platelet reactivity (HTPR) in this cohort. We found that local ancestry at the TSS of three genes, IRS-1, ABCB1 and KDR were nominally associated with PRU, and local ancestry-adjusted SNP association identified variants in ITGA2 associated to increased PRU. These finding help to explain the variability in drug response seen in African Americans, especially as few studies on genes outside of CYP2C19 has been conducted in this population.
Identifiants
pubmed: 36540979
pii: 9789811270611_0021
pmc: PMC9782753
mid: NIHMS1852991
Substances chimiques
Clopidogrel
A74586SNO7
Platelet Aggregation Inhibitors
0
Ticlopidine
OM90ZUW7M1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
221-232Subventions
Organisme : NHGRI NIH HHS
ID : U24 HG010615
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD010723
Pays : United States
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