PMID- 33370281
OWN - NLM
STAT- MEDLINE
DCOM- 20210115
LR  - 20210115
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 15
IP  - 12
DP  - 2020
TI  - Clopidogrel responder status is uninfluenced by CYP2C19*2 in Danish patients with 
      stroke.
PG  - e0236260
LID - 10.1371/journal.pone.0236260 [doi]
LID - e0236260
AB  - BACKGROUND: Antiplatelet therapy is a cornerstone of secondary stroke prevention, 
      but the responsiveness to antiplatelet medication varies among patients. 
      Clopidogrel is a pro-drug that requires hepatic transformation to reach its 
      active metabolite. Single nucleotide polymorphisms (SNPs) in key enzymes or the 
      target adenosine diphosphate (ADP) receptor on the platelet surface are believed 
      to be involved in clopidogrel-mediated platelet inhibition and decreased 
      antiplatelet effect with high-on-treatment platelet reactivity (HTPR). OBJECTIVE: 
      This study investigated whether specific SNPs in key hepatic enzymes (CYP2C19*2, 
      *3, *17, CYP3A4*1G, and NR1I2) or the ADP receptor (PR2Y12) are associated with 
      HTPR to clopidogrel. PATIENTS & METHODS: This observational study included 
      patients with ischemic stroke (IS) and transient ischemic attacks (TIAs) 
      receiving clopidogrel at a dose of 75 mg/day. Patients were genotyped for eight 
      different SNPs in the genes encoding CYP2C19, CYP3A4, NR1I2, and the P2Y12 
      receptor. RESULTS: Of the 103 patients that were included, 30.7% carried the 
      CYP2C19*2 allele and had higher platelet reaction unit (PRU) values than 
      non-carriers, but no patients showed HTPR. Carriers of the *17 allele had higher 
      platelet inhibition but showed no difference in PRU values compared with 
      non-carriers. The remaining SNPs were neither associated with PRU nor with 
      platelet inhibition. CONCLUSIONS: Patients with IS and TIAs treated with 75 mg 
      clopidogrel/day do not have HTPR. A genetic analysis of CYP2C19*2, *3, *17, 
      CYP3A4*1G, and NR1I2 revealed no associations with clopidogrel HTPR. CYP2C19*2 
      carriers and patients with HTPR in the acute phase after ischemic stroke or 
      transient ischemic attacks exhibit higher PRU values, but not long-term treatment 
      HTPR.
FAU - Rath, Charlotte Lutzhoft
AU  - Rath CL
AUID- ORCID: 0000-0002-3011-0070
AD  - Neurovascular Centre, Department of Neurology, Zealand University Hospital, 
      Roskilde, Denmark.
FAU - Jorgensen, Niklas Rye
AU  - Jorgensen NR
AD  - Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 
      Copenhagen, Denmark.
AD  - OPEN, Odense Patient data Explorative Network, Odense University 
      Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, 
      Denmark.
FAU - Wienecke, Troels
AU  - Wienecke T
AD  - Neurovascular Centre, Department of Neurology, Zealand University Hospital, 
      Roskilde, Denmark.
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20201228
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - A74586SNO7 (Clopidogrel)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Clopidogrel/*therapeutic use
MH  - Cytochrome P-450 CYP2C19/*genetics
MH  - Denmark
MH  - Female
MH  - Gene Frequency
MH  - Genotype
MH  - Humans
MH  - Ischemic Stroke/genetics/*prevention & control
MH  - Male
MH  - Middle Aged
MH  - Platelet Aggregation Inhibitors/*therapeutic use
MH  - *Polymorphism, Single Nucleotide
MH  - Secondary Prevention
PMC - PMC7769274
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/12/29 06:00
MHDA- 2021/01/16 06:00
PMCR- 2020/12/28
CRDT- 2020/12/28 17:10
PHST- 2019/11/08 00:00 [received]
PHST- 2020/07/02 00:00 [accepted]
PHST- 2020/12/28 17:10 [entrez]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/01/16 06:00 [medline]
PHST- 2020/12/28 00:00 [pmc-release]
AID - PONE-D-19-31152 [pii]
AID - 10.1371/journal.pone.0236260 [doi]
PST - epublish
SO  - PLoS One. 2020 Dec 28;15(12):e0236260. doi: 10.1371/journal.pone.0236260. 
      eCollection 2020.