PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study.
<h4>Background and purpose</h4>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 clopido...
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2021
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oai:doaj.org-article:ee85d159b18f4b65aca124675715358b2021-12-02T20:18:42ZPON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study.1932-620310.1371/journal.pone.0254067https://doaj.org/article/ee85d159b18f4b65aca124675715358b2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254067https://doaj.org/toc/1932-6203<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Koji TanakaShoji MatsumotoGulibahaer AinidingIchiro NakaharaHidehisa NishiTetsuya HashimotoTsuyoshi OhtaNobutake SadamasaRyota IshibashiMasanori GomiMakoto SakaHaruka MiyataSadayoshi WatanabeTakuya OkataKazutaka SonodaJunpei KogeKyoko M IinumaKonosuke FurutaIzumi NagataKeitaro MatsuoTakuya MatsushitaNoriko IsobeRyo YamasakiJun-Ichi KiraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0254067 (2021) |
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Medicine R Science Q Koji Tanaka Shoji Matsumoto Gulibahaer Ainiding Ichiro Nakahara Hidehisa Nishi Tetsuya Hashimoto Tsuyoshi Ohta Nobutake Sadamasa Ryota Ishibashi Masanori Gomi Makoto Saka Haruka Miyata Sadayoshi Watanabe Takuya Okata Kazutaka Sonoda Junpei Koge Kyoko M Iinuma Konosuke Furuta Izumi Nagata Keitaro Matsuo Takuya Matsushita Noriko Isobe Ryo Yamasaki Jun-Ichi Kira PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study. |
| description |
<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Koji Tanaka Shoji Matsumoto Gulibahaer Ainiding Ichiro Nakahara Hidehisa Nishi Tetsuya Hashimoto Tsuyoshi Ohta Nobutake Sadamasa Ryota Ishibashi Masanori Gomi Makoto Saka Haruka Miyata Sadayoshi Watanabe Takuya Okata Kazutaka Sonoda Junpei Koge Kyoko M Iinuma Konosuke Furuta Izumi Nagata Keitaro Matsuo Takuya Matsushita Noriko Isobe Ryo Yamasaki Jun-Ichi Kira |
| author_facet |
Koji Tanaka Shoji Matsumoto Gulibahaer Ainiding Ichiro Nakahara Hidehisa Nishi Tetsuya Hashimoto Tsuyoshi Ohta Nobutake Sadamasa Ryota Ishibashi Masanori Gomi Makoto Saka Haruka Miyata Sadayoshi Watanabe Takuya Okata Kazutaka Sonoda Junpei Koge Kyoko M Iinuma Konosuke Furuta Izumi Nagata Keitaro Matsuo Takuya Matsushita Noriko Isobe Ryo Yamasaki Jun-Ichi Kira |
| author_sort |
Koji Tanaka |
| title |
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_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_sort |
pon1 q192r is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: a prospective single-center cohort study. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/ee85d159b18f4b65aca124675715358b |
| work_keys_str_mv |
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