title: Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy.
abstract: OBJECTIVE
  CYP2C19*2 loss-of-function allele in Caucasians may be associated with wide interindividual variability in platelet response to clopidogrel, and the incidence of gene mutation varies with racial differences, especially between Asians and Caucasians. The aim was to examine the impact of CYP2C19 genotype on the residual platelet reactivity in Japanese patients with coronary heart disease (CHD) during antiplatelet therapy.
  
  
  RESULTS
  We measured the CYP2C19 genotype and platelet aggregation in 201 patients with stable CHD. Moreover, we examined the relation of CYP2C19 polymorphism to cardiovascular events in 98 patients treated with stent implantation. The distribution of CYP2C19 genotype was 37%, 33%, 11%, 11%, 7%, and 1% in CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Residual platelet reactivity was lower in patients during dual antiplatelet therapy (DAT) than in those with aspirin (3975 ± 1569 aggregation units minute (AU min) vs 5850 ± 938 AU min, p<0.05). In the DAT group, the platelet reactivity decreased significantly in the wild-type homozygotes (CYP2C19*1/*1), subsequently in the *2, or *3 heterozygotes (*1/*2, *1/*3), and was not well inhibited in the *2, and/or *3 homozygotes (*2/*2, *2/*3, *3/*3; 3194 ± 1570 AU min, 4148 ± 1400 AU min, and 5088 ± 1080 AU min, respectively). However, when the duration of DAT was used to divide subjects into 2 groups, <7 days, and >7 days, patients carrying the variant allele showed significantly decreased platelet reactivities at >7 days compared with those at <7 days. Moreover, the incidence of cardiovascular events was higher in patients carrying at least one variant allele than in wild-type homozygotes.
  
  
  CONCLUSIONS
  CYP2C19 polymorphism may be associated with high residual platelet reactivity and the occurrence of cardiovascular events.
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Hokimoto
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Chitose
authors.forename: Kazunori
authors.initials: K
authors.lastname: Morita
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ono
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tsujita
authors.forename: Tomohide
authors.initials: T
authors.lastname: Abe
authors.forename: Mariko
authors.initials: M
authors.lastname: Deguchi
authors.forename: Haruna
authors.initials: H
authors.lastname: Miyagawa
authors.forename: Junji
authors.initials: J
authors.lastname: Saruwatari
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sumida
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D002318:Cardiovascular Diseases / Q000235:genetics; D000077144:Clopidogrel; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy*; D065731:Cytochrome P-450 CYP2C19; D057510:Endovascular Procedures; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011110:Polymorphism, Genetic; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine