Key result
Specific local ancestry and ITGA2 variants link to P2Y12 reaction units in African Americans on clopidogrel.
Why the study?
Pharmacogenomics has long lacked dedicated studies in African Americans, leading to a lack of in-depth data on population-specific variation contributing to clopidogrel response.
Does global and local ancestry affect clopidogrel response (PRU and HTPR) in African American patients?
Cohort (n=167)
Yes
Does global and local ancestry affect clopidogrel response (PRU and HTPR) in African American patients?
Genetic variants in ITGA2 and local ancestry at specific genes are associated with variability in clopidogrel response among African Americans.
Associations with PRU should not change clopidogrel prescribing; hypothesis-generating for ancestry effects in African American pharmacogenomics.
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.
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Yang et al. (2022) conducted a cohort in Patients on steady state clopidogrel (n=167). Clopidogrel was evaluated on P2Y12 reaction units (PRU) and high on-treatment platelet reactivity (HTPR). Local ancestry at the TSS of IRS-1, ABCB1, and KDR, and variants in ITGA2, were associated with P2Y12 reaction units in African American patients on steady-state clopidogrel.
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