Association of platelet ITGA2B and ITGB3 polymorphisms with ex vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects.
Ticagrelor (TIC) is the first reversible P2Y12 receptor antagonist that exhibits rapid antiplatelet effect by indirect inhibition of the GPIIb/IIIa complex. Polymorphisms in genes coding GPIIb/IIIa, namely ITGA2B and ITGB3, are associated with aspirin resistance and risk for thrombotic diseases. We assessed whether ITGA2B and ITGB3 polymorphisms can influence the ex vivo antiplatelet activity of ticagrelor in Chinese population. A total of 196 healthy Chinese male individuals were recruited. ADP-induced platelet aggregation was determined using optical aggregometry at baseline and after incubation of the platelet-rich plasma with 15 and 50 μM ticagrelor, respectively. Single nucleotide polymorphisms in ITGA2B (rs5911 G>T) and ITGB3 (rs4642 A>G and rs4634 G>A) were genotyped by sequencing. TIC at both concentrations of 15 and 50 μM decreased ADP-induced platelet aggregation significantly (P < 0.05, respectively). As compared to ITGA2B rs5911 GG homozygotes, individuals with the rs5911 TG genotype showed significantly increased inhibition of platelet aggregation (IPA) by both 15 and 50 μM ticagrelor incubation (P < 0.05, respectively). Neither rs4642 nor rs4634 polymorphism affected ticagrelor-induced IPA. We suggest that the ITGA2B rs5911 GG genotype is associated with decreased ex vivo antiplatelet activity of ticagrelor in healthy Chinese male subjects.
Institute of Clinical Pharmacology, Central South University, Changsha, 410078, Hunan, China.
Mu-Peng
MP
Li
Yan
Y
Xiong
An
A
Xu
Ji-Peng
JP
Zhou
Jie
J
Tang
Zan-Ling
ZL
Zhang
Hong-Hao
HH
Zhou
Wei
W
Zhang
Xiao-Ping
XP
Chen
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology*; D000077486:Ticagrelor; D055815:Young Adult
C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039661:Integrin beta3; D058919:Purinergic P2 Receptor Antagonists; D000244:Adenosine Diphosphate; D000077486:Ticagrelor; D000241:Adenosine