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

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 un...

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Autores principales: Tanaka, Koji, Matsumoto, Shoji, Ainiding, Gulibahaer, Nakahara, Ichiro, Nishi, Hidehisa, Hashimoto, Tetsuya, Ohta, Tsuyoshi, Sadamasa, Nobutake, Ishibashi, Ryota, Gomi, Masanori, Saka, Makoto, Miyata, Haruka, Watanabe, Sadayoshi, Okata, Takuya, Sonoda, Kazutaka, Koge, Junpei, Iinuma, Kyoko M., Furuta, Konosuke, Nagata, Izumi, Matsuo, Keitaro, Matsushita, Takuya, Isobe, Noriko, Yamasaki, Ryo, Kira, Jun-ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341610/
https://www.ncbi.nlm.nih.gov/pubmed/34351918
http://dx.doi.org/10.1371/journal.pone.0254067
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author Tanaka, Koji
Matsumoto, Shoji
Ainiding, Gulibahaer
Nakahara, Ichiro
Nishi, Hidehisa
Hashimoto, Tetsuya
Ohta, Tsuyoshi
Sadamasa, Nobutake
Ishibashi, Ryota
Gomi, Masanori
Saka, Makoto
Miyata, Haruka
Watanabe, Sadayoshi
Okata, Takuya
Sonoda, Kazutaka
Koge, Junpei
Iinuma, Kyoko M.
Furuta, Konosuke
Nagata, Izumi
Matsuo, Keitaro
Matsushita, Takuya
Isobe, Noriko
Yamasaki, Ryo
Kira, Jun-ichi
author_facet Tanaka, Koji
Matsumoto, Shoji
Ainiding, Gulibahaer
Nakahara, Ichiro
Nishi, Hidehisa
Hashimoto, Tetsuya
Ohta, Tsuyoshi
Sadamasa, Nobutake
Ishibashi, Ryota
Gomi, Masanori
Saka, Makoto
Miyata, Haruka
Watanabe, Sadayoshi
Okata, Takuya
Sonoda, Kazutaka
Koge, Junpei
Iinuma, Kyoko M.
Furuta, Konosuke
Nagata, Izumi
Matsuo, Keitaro
Matsushita, Takuya
Isobe, Noriko
Yamasaki, Ryo
Kira, Jun-ichi
author_sort Tanaka, Koji
collection PubMed
description 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.
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spelling pubmed-83416102021-08-06 PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study Tanaka, Koji Matsumoto, Shoji Ainiding, Gulibahaer Nakahara, Ichiro Nishi, Hidehisa Hashimoto, Tetsuya Ohta, Tsuyoshi Sadamasa, Nobutake Ishibashi, Ryota Gomi, Masanori Saka, Makoto Miyata, Haruka Watanabe, Sadayoshi Okata, Takuya Sonoda, Kazutaka Koge, Junpei Iinuma, Kyoko M. Furuta, Konosuke Nagata, Izumi Matsuo, Keitaro Matsushita, Takuya Isobe, Noriko Yamasaki, Ryo Kira, Jun-ichi PLoS One Research Article 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. Public Library of Science 2021-08-05 /pmc/articles/PMC8341610/ /pubmed/34351918 http://dx.doi.org/10.1371/journal.pone.0254067 Text en © 2021 Tanaka et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tanaka, Koji
Matsumoto, Shoji
Ainiding, Gulibahaer
Nakahara, Ichiro
Nishi, Hidehisa
Hashimoto, Tetsuya
Ohta, Tsuyoshi
Sadamasa, Nobutake
Ishibashi, Ryota
Gomi, Masanori
Saka, Makoto
Miyata, Haruka
Watanabe, Sadayoshi
Okata, Takuya
Sonoda, Kazutaka
Koge, Junpei
Iinuma, Kyoko M.
Furuta, Konosuke
Nagata, Izumi
Matsuo, Keitaro
Matsushita, Takuya
Isobe, Noriko
Yamasaki, Ryo
Kira, Jun-ichi
PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study
title PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study
title_full PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study
title_fullStr PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study
title_full_unstemmed PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study
title_short PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study
title_sort pon1 q192r is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: a prospective single-center cohort study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341610/
https://www.ncbi.nlm.nih.gov/pubmed/34351918
http://dx.doi.org/10.1371/journal.pone.0254067
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