title: Plasma miR-142 accounting for the missing heritability of CYP3A4/5 functionality is associated with pharmacokinetics of clopidogrel.
abstract: To investigate whether plasma miRNAs targeting CYP3A4/5 have an impact on the variance of pharmacokinetics of clopidogrel.
  
  
  
  The contribution of 13 miRNAs to the CYP3A4/5 gene expression and activity was investigated in 55 liver tissues. The association between plasma miRNAs targeting CYP3A4/5 mRNA and clopidogrel pharmacokinetics was analyzed in 31 patients with coronary heart disease who received 300 mg loading dose of clopidogrel.
  
  
  
  Among 13 miRNAs, miR-142 was accounting for 12.2% (p = 0.002) CYP3A4 mRNA variance and 9.4% (p = 0.005) CYP3A5 mRNA variance, respectively. Plasma miR-142 was negatively associated with H4 Cmax (r = -0.5269; p = 0.0040) and associated with H4 AUC0-4h (r = -0.4986; p = 0.0069) after 300 mg loading dose of clopidogrel in coronary heart disease patients.
  
  
  
  miR-142 could account for a part of missing heritability of CYP3A4/5 functionality related to clopidogrel activation.
authors.affiliation: School of Pharmacy, Guangdong Metabolic Diseases Research Center of Integrated Chinese & Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.|Medical Research Center of Guangdong General Hospital, Guangzhou, China.
authors.forename: Qian-Jie
authors.initials: QJ
authors.lastname: Tang
authors.affiliation: Department of Biliary & Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hao-Ming
authors.initials: HM
authors.lastname: Lin
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.|Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: He
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.|Department of Pharmacy, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ju-E
authors.initials: JE
authors.lastname: Liu
authors.affiliation: Department of Biliary & Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Li
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.|Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Zhong
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tang
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.
authors.forename: Jin-Xiu
authors.initials: JX
authors.lastname: Meng
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.
authors.forename: Meng-Zhen
authors.initials: MZ
authors.lastname: Zhang
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Li
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.|Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Ji-Yan
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, China.|Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Shi-Long
authors.initials: SL
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Guangdong Metabolic Diseases Research Center of Integrated Chinese & Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Lai-You
authors.initials: LY
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000032:analysis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D000077144:Clopidogrel; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine
keywords: CYP3A; clopidogrel; microRNA; pharmacokinetics