title: The association of ABCC3 promoter methylation with clopidogrel response in Chinese ischemic stroke patients.
abstract: Multidrug resistance protein 3 (MRP3), encoded by ABCC3, is an ATP-dependent efflux pump mediating the transport of many drugs, implicated in clopidogrel resistance. This study enrolled 87 ischemic stroke patients with CYP2C1 9*1/*1 genotype, who received clopidogrel (75 mg/day) for at least 5 days before discharge. The maximum platelet aggregation (MPA) was measured by light transmittance aggregometry (LTA) to assess platelet function. Whole blood samples were obtained to evaluate the ABCC3 promoter methylation and mRNA expression of ABCC3. Pyrosequencing was carried out to investigate ABCC3 methylation and ABCC3 mRNA expression was evaluated by qPCR. The ABCC3 methylation was neither significantly different among the four MPA quartile groups (P = 0.275) nor independently associated with MPA values (R = 0.100, P = 0.358). However, the ABCC3 promoter methylation status in 87 clinical samples from patients correlated inversely with the expression of ABCC3 (R = - 0.854, P < 0.001). In addition, the ABCC3 expression was neither significantly different among the four quartile groups (P = 0.499) nor independently associated with MPA values (R = 0.060, P = 0.582). ABCC3 promoter methylation does not seem to exhibit any impact on MPA and clopidogrel response at all.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Jun-Shan
authors.initials: JS
authors.lastname: Zhou
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: Zhang
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Tian
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zou
mesh_terms: D000368:Aged; D044466:Asian People; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000096:biosynthesis / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D013988:Ticlopidine; C114462:multidrug resistance-associated protein 3