PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study

Autor: Izumi Nagata, Hidehisa Nishi, Keitaro Matsuo, Nobutake Sadamasa, Takuya Matsushita, Tetsuya Hashimoto, Ichiro Nakahara, Koji Tanaka, Ryota Ishibashi, Noriko Isobe, Makoto Saka, Kyoko Iinuma, Ryo Yamasaki, Jun Ichi Kira, Konosuke Furuta, Gulibahaer Ainiding, Takuya Okata, Haruka Miyata, Sadayoshi Watanabe, Tsuyoshi Ohta, Masanori Gomi, Junpei Koge, Kazutaka Sonoda, Shoji Matsumoto
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Physiology
Single Nucleotide Polymorphisms
Hematocrit
Single Center
Antiplatelet Therapy
Gastroenterology
Biochemistry
Vascular Medicine
Neurosurgical Procedures
Animal Cells
Medicine and Health Sciences
Metabolites
Prospective Studies
Multidisciplinary
medicine.diagnostic_test
Pharmaceutics
Hematology
Middle Aged
Clopidogrel
Lipids
Body Fluids
Blood
Cholesterol
Medicine
Female
Anatomy
Cellular Types
Cohort study
medicine.drug
Research Article
Platelets
Blood Platelets
medicine.medical_specialty
Science
Mutation
Missense
Single-nucleotide polymorphism
CYP2C19
Drug Therapy
Internal medicine
Thromboembolism
medicine
Genetics
Humans
Alleles
Aged
Blood Cells
business.industry
Aryldialkylphosphatase
Biology and Life Sciences
Odds ratio
Cell Biology
Platelet Activation
Confidence interval
Blood Counts
Metabolism
Amino Acid Substitution
Genetic Loci
business
Zdroj: PLoS ONE, Vol 16, Iss 8, p e0254067 (2021)
PLoS ONE, Vol 16, Iss 8 (2021)
PLoS ONE
ISSN: 1932-6203
Popis: Background and purpose The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. Methods Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208. Results Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03–3.76) and corrected PRU (OR 2.34, 95% CI 1.21–4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele. Conclusions Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.
Databáze: OpenAIRE
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