Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity.
Aspirin prevents the production of thromboxane A2 (TXA2) by irreversibly inhibiting platelet cyclooxygenase, exhibiting antiplatelet actions. This agent has been reported to prevent relapse in patients with ischemic heart disease or cerebral infarction via this action mechanism. However, there are individual differences in this action, and aspirin is not effective in some patients, which is referred to as 'aspirin resistance'. In this study, we analyzed laboratory aspirin resistance by platelet aggregation in 110 healthy adult Japanese males using 24 single-nucleotide polymorphisms (SNPs) of nine genes involved in platelet aggregation/hemorrhage. Among SNPs involved in platelet aggregation, aspirin was less effective for 924T homozygote of a TXA2 receptor, 924T>C, and 1018C homozygote of a platelet membrane glycoprotein GPIbalpha, 1018C>T, suggesting that 924T and 1018C alleles are involved in aspirin resistance.
Fujiwara
T
T
Otsuka Pharmaceutical Co., Ltd., Osaka, Japan. fujiwaratu@otsuka.jp
Ikeda
M
M
Esumi
K
K
Fujita
T D
TD
Kono
M
M
Tokushige
H
H
Hatoyama
T
T
Maeda
T
T
Asai
T
T
Ogawa
T
T
Katsumata
T
T
Sasaki
S
S
Suzuki
E
E
Suzuki
M
M
Hino
F
F
Fujita
T K
TK
Zaima
H
H
Shimada
M
M
Sugawara
T
T
Tsuzuki
Y
Y
Hashimoto
Y
Y
Hishigaki
H
H
Horimoto
S
S
Miyajima
N
N
Yamamoto
T
T
Imagawa
K
K
Sesoko
S
S
Fujisawa
Y
Y
D000328:Adult; D044466:Asian People; D001241:Aspirin / Q000097:blood / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000494:pharmacology*; D019038:Platelet Glycoprotein GPIb-IX Complex; D020641:Polymorphism, Single Nucleotide; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics*; D012016:Reference Values; D020156:Salicylic Acid / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C094990:adhesion receptor; D013929:Thromboxane B2; D020156:Salicylic Acid; D001241:Aspirin