DAPT inhibitor

Association of α2A-Adrenergic Receptor Genetic Variants with Platelet Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing Percutaneous Coronary Intervention

Abstract
Objective: The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism influences how individuals respond to antiplatelet treatment during sympathetic stimulation. This study aimed to examine how variations in the ADRA2A gene affect platelet reactivity in Chinese patients undergoing dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI).

Methods: Between March 2011 and March 2013, this prospective, single-center observational study in China enrolled 1,024 patients. Four single nucleotide polymorphisms (SNPs) of the ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19*2 were analyzed using ligase detection reaction (LDR), while adenosine diphosphate (ADP) inhibition was measured via thromboelastography (TEG®).

Results: The minor allele frequencies of ADRA2A SNPs were relatively high. Platelet ADP inhibition varied significantly among patients with rs11195419 (adjusted P = 0.022) and rs3750625 (adjusted P = 0.016). Those with homozygous alleles exhibited the lowest ADP inhibition. In contrast, no significant differences were found for rs553668 and rs13306146. Multivariate analysis identified rs11195419 (P = 0.033), rs3750625 (P = 0.020), and CYP2C19*2 (P = 0.002) as independent predictors of ADP inhibition. Subgroup analysis by sex revealed significant associations between rs11195419 (P = 0.003) and rs3750625 (P = 0.002) and ADP inhibition in males, but not in females.

Conclusion: Variations in the ADRA2A gene were linked to ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, with a more pronounced effect observed in DAPT inhibitor males.