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Relationship between CYP2C19 Polymorphism and Clopidogrel Resistance in Patients with Coronary Heart Disease and Ischemic Stroke in China

Objective. Clopidogrel is widely used for preventing ischemic complications related to cardiovascular diseases. However, many patients experience clopidogrel resistance (CR). The polymorphisms of CYP2C19 have been implicated in CR, but CYP2C19 polymorphism considerably varies with both ethnic group...

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Published in:Genetics Research 2022, Vol.2022, p.1901256-11
Main Authors: Chang, Rong, Zhou, Wenqin, Ye, Yi, Zhang, Xiaofei, Liu, Yanmin, Wu, Jinchun
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Zhou, Wenqin
Ye, Yi
Zhang, Xiaofei
Liu, Yanmin
Wu, Jinchun
description Objective. Clopidogrel is widely used for preventing ischemic complications related to cardiovascular diseases. However, many patients experience clopidogrel resistance (CR). The polymorphisms of CYP2C19 have been implicated in CR, but CYP2C19 polymorphism considerably varies with both ethnic group and geographical location. This study aimed to investigate the association between CYP2C19 polymorphisms and clopidogrel resistance (CR) in patients with coronary heart disease and ischemic stroke among Han and Tibetan populations in Qinghai Province, China. Methods. From June 2019 to January 2020, patients who were diagnosed with coronary heart disease or cerebral infarction in internal medicine of Qinghai Provincial People’s Hospital and had taken dual antiplatelet drugs were included in this study. Blood was collected and routine items were completed. Whole exome sequencing was performed for CYP2C19 genetic polymorphisms of CYP2C19∗2 (rs4244285), CYP2C19∗3 (rs4986893), and CYP2C19∗17 (rs12248560). Results. A total of 91 patients with coronary heart disease or cerebral infarction (67 Han people (65.99 ± 12.25 years old) and 24 Tibetan (63.6324 Tib years old)) including 52 cases with CR and 39 cases with non-CR were enrolled in this study. For the Han population, the differences in age, glycosylated hemoglobin, activated partial thromboplastin time (APTT), gender, aspirin resistance, and diabetes were significant between the CR and non-CR groups. For the Tibetan population, the two groups showed no significant difference in all indicators. There was no significant difference between CR and non-CR groups for all genotypes (CYP2C19 ∗2, ∗3, and ∗17) in either Han or Tibetan populations. For the Han populations, age, APTT, and aspirin resistance were significantly correlated with CR. Conclusion. The present study indicated that CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 alleles were not correlated with CR for both Han and Tibetan populations in Qinghai Province, while age, APTT, and aspirin resistance were independent risk factors of CR in this region.
doi_str_mv 10.1155/2022/1901256
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Clopidogrel is widely used for preventing ischemic complications related to cardiovascular diseases. However, many patients experience clopidogrel resistance (CR). The polymorphisms of CYP2C19 have been implicated in CR, but CYP2C19 polymorphism considerably varies with both ethnic group and geographical location. This study aimed to investigate the association between CYP2C19 polymorphisms and clopidogrel resistance (CR) in patients with coronary heart disease and ischemic stroke among Han and Tibetan populations in Qinghai Province, China. Methods. From June 2019 to January 2020, patients who were diagnosed with coronary heart disease or cerebral infarction in internal medicine of Qinghai Provincial People’s Hospital and had taken dual antiplatelet drugs were included in this study. Blood was collected and routine items were completed. Whole exome sequencing was performed for CYP2C19 genetic polymorphisms of CYP2C19∗2 (rs4244285), CYP2C19∗3 (rs4986893), and CYP2C19∗17 (rs12248560). Results. A total of 91 patients with coronary heart disease or cerebral infarction (67 Han people (65.99 ± 12.25 years old) and 24 Tibetan (63.6324 Tib years old)) including 52 cases with CR and 39 cases with non-CR were enrolled in this study. For the Han population, the differences in age, glycosylated hemoglobin, activated partial thromboplastin time (APTT), gender, aspirin resistance, and diabetes were significant between the CR and non-CR groups. For the Tibetan population, the two groups showed no significant difference in all indicators. There was no significant difference between CR and non-CR groups for all genotypes (CYP2C19 ∗2, ∗3, and ∗17) in either Han or Tibetan populations. For the Han populations, age, APTT, and aspirin resistance were significantly correlated with CR. Conclusion. The present study indicated that CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 alleles were not correlated with CR for both Han and Tibetan populations in Qinghai Province, while age, APTT, and aspirin resistance were independent risk factors of CR in this region.</description><identifier>ISSN: 1469-5073</identifier><identifier>ISSN: 0016-6723</identifier><identifier>EISSN: 1469-5073</identifier><identifier>DOI: 10.1155/2022/1901256</identifier><identifier>PMID: 36325266</identifier><language>eng</language><publisher>England: Hindawi</publisher><subject>Age ; Aged ; Aspirin ; Blood ; Blood platelets ; Cardiovascular disease ; Cardiovascular diseases ; Cerebral Infarction ; China ; Clopidogrel ; Clopidogrel - therapeutic use ; Complications ; Coronary artery disease ; Coronary Disease - drug therapy ; Coronary Disease - genetics ; Cytochrome P-450 CYP2C19 - genetics ; Diabetes mellitus ; DNA methylation ; Gene polymorphism ; Genotype ; Genotypes ; Geographical distribution ; Geographical locations ; Heart ; Heart diseases ; Hemoglobin ; Humans ; Infarction ; Ischemia ; Ischemic Stroke ; Metabolites ; Middle Aged ; Minority &amp; ethnic groups ; Myocardial infarction ; Patients ; Polymorphism ; Polymorphism, Genetic - genetics ; Population studies ; Populations ; Resistance factors ; Risk analysis ; Risk factors ; Signal transduction ; Statistical analysis ; Stroke ; Thromboplastin ; Ticlopidine</subject><ispartof>Genetics Research, 2022, Vol.2022, p.1901256-11</ispartof><rights>Copyright © 2022 Rong Chang et al.</rights><rights>Copyright © 2022 Rong Chang et al. 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Clopidogrel is widely used for preventing ischemic complications related to cardiovascular diseases. However, many patients experience clopidogrel resistance (CR). The polymorphisms of CYP2C19 have been implicated in CR, but CYP2C19 polymorphism considerably varies with both ethnic group and geographical location. This study aimed to investigate the association between CYP2C19 polymorphisms and clopidogrel resistance (CR) in patients with coronary heart disease and ischemic stroke among Han and Tibetan populations in Qinghai Province, China. Methods. From June 2019 to January 2020, patients who were diagnosed with coronary heart disease or cerebral infarction in internal medicine of Qinghai Provincial People’s Hospital and had taken dual antiplatelet drugs were included in this study. Blood was collected and routine items were completed. Whole exome sequencing was performed for CYP2C19 genetic polymorphisms of CYP2C19∗2 (rs4244285), CYP2C19∗3 (rs4986893), and CYP2C19∗17 (rs12248560). Results. A total of 91 patients with coronary heart disease or cerebral infarction (67 Han people (65.99 ± 12.25 years old) and 24 Tibetan (63.6324 Tib years old)) including 52 cases with CR and 39 cases with non-CR were enrolled in this study. For the Han population, the differences in age, glycosylated hemoglobin, activated partial thromboplastin time (APTT), gender, aspirin resistance, and diabetes were significant between the CR and non-CR groups. For the Tibetan population, the two groups showed no significant difference in all indicators. There was no significant difference between CR and non-CR groups for all genotypes (CYP2C19 ∗2, ∗3, and ∗17) in either Han or Tibetan populations. For the Han populations, age, APTT, and aspirin resistance were significantly correlated with CR. Conclusion. The present study indicated that CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 alleles were not correlated with CR for both Han and Tibetan populations in Qinghai Province, while age, APTT, and aspirin resistance were independent risk factors of CR in this region.</description><subject>Age</subject><subject>Aged</subject><subject>Aspirin</subject><subject>Blood</subject><subject>Blood platelets</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cerebral Infarction</subject><subject>China</subject><subject>Clopidogrel</subject><subject>Clopidogrel - therapeutic use</subject><subject>Complications</subject><subject>Coronary artery disease</subject><subject>Coronary Disease - drug therapy</subject><subject>Coronary Disease - genetics</subject><subject>Cytochrome P-450 CYP2C19 - genetics</subject><subject>Diabetes mellitus</subject><subject>DNA methylation</subject><subject>Gene polymorphism</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Geographical distribution</subject><subject>Geographical locations</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Infarction</subject><subject>Ischemia</subject><subject>Ischemic Stroke</subject><subject>Metabolites</subject><subject>Middle Aged</subject><subject>Minority &amp; ethnic groups</subject><subject>Myocardial infarction</subject><subject>Patients</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Population studies</subject><subject>Populations</subject><subject>Resistance factors</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Signal transduction</subject><subject>Statistical analysis</subject><subject>Stroke</subject><subject>Thromboplastin</subject><subject>Ticlopidine</subject><issn>1469-5073</issn><issn>0016-6723</issn><issn>1469-5073</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kktv1DAURiMEoqWwY40ssUGCoX473lRC4dGRKjEqsGBlOc7NxEMSD3aGUX8C_xrPg6plwcqWfXx07_VXFM8JfkuIEOcUU3pONCZUyAfFKeFSzwRW7OGd_UnxJKUVxoThUj0uTphkVFApT4vf19DbyYcxdX6Napi2ACOqvi9oRTRahP5mCHHd-TQgOzao6sPaN2EZoUfXkHya7OgA-REtsgXGKaGtnzpUhRhGG2_QJdg4ofc-gU2wV8yT62DwDn2ZYvixf1t1frRPi0et7RM8O65nxbePH75Wl7Orz5_m1burmROETzPdSi25xqxtOW1A1VaAto1zHAsqbE1BSRBKliVILYTTnCstwTKLRUsaxs6K-cHbBLsy6-iHXKcJ1pv9QYhLk0v2rgejndB1LeqSMc4dNGVrKSe2ZbwpnSQuuy4OrvWmHqBxeQDR9vek929G35ll-GW0JFIqlQWvjoIYfm4gTWbwyUHf2xHCJhmqGFFEc8Iz-vIfdBU2ccyj2lGYCIXVjnpzoFwMKUVob4sh2OzyYnZ5Mce8ZPzF3QZu4b8BycDrA5C_qLFb_3_dH13KyMc</recordid><startdate>2022</startdate><enddate>2022</enddate><creator>Chang, Rong</creator><creator>Zhou, Wenqin</creator><creator>Ye, Yi</creator><creator>Zhang, Xiaofei</creator><creator>Liu, Yanmin</creator><creator>Wu, Jinchun</creator><general>Hindawi</general><general>Hindawi Limited</general><general>Hindawi - Cambridge University Press</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PADUT</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-6855-4710</orcidid><orcidid>https://orcid.org/0000-0002-5657-421X</orcidid><orcidid>https://orcid.org/0000-0003-4837-2615</orcidid><orcidid>https://orcid.org/0000-0002-5458-6612</orcidid><orcidid>https://orcid.org/0000-0002-3778-1563</orcidid><orcidid>https://orcid.org/0000-0002-0754-8584</orcidid></search><sort><creationdate>2022</creationdate><title>Relationship between CYP2C19 Polymorphism and Clopidogrel Resistance in Patients with Coronary Heart Disease and Ischemic Stroke in China</title><author>Chang, Rong ; 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Clopidogrel is widely used for preventing ischemic complications related to cardiovascular diseases. However, many patients experience clopidogrel resistance (CR). The polymorphisms of CYP2C19 have been implicated in CR, but CYP2C19 polymorphism considerably varies with both ethnic group and geographical location. This study aimed to investigate the association between CYP2C19 polymorphisms and clopidogrel resistance (CR) in patients with coronary heart disease and ischemic stroke among Han and Tibetan populations in Qinghai Province, China. Methods. From June 2019 to January 2020, patients who were diagnosed with coronary heart disease or cerebral infarction in internal medicine of Qinghai Provincial People’s Hospital and had taken dual antiplatelet drugs were included in this study. Blood was collected and routine items were completed. Whole exome sequencing was performed for CYP2C19 genetic polymorphisms of CYP2C19∗2 (rs4244285), CYP2C19∗3 (rs4986893), and CYP2C19∗17 (rs12248560). Results. A total of 91 patients with coronary heart disease or cerebral infarction (67 Han people (65.99 ± 12.25 years old) and 24 Tibetan (63.6324 Tib years old)) including 52 cases with CR and 39 cases with non-CR were enrolled in this study. For the Han population, the differences in age, glycosylated hemoglobin, activated partial thromboplastin time (APTT), gender, aspirin resistance, and diabetes were significant between the CR and non-CR groups. For the Tibetan population, the two groups showed no significant difference in all indicators. There was no significant difference between CR and non-CR groups for all genotypes (CYP2C19 ∗2, ∗3, and ∗17) in either Han or Tibetan populations. For the Han populations, age, APTT, and aspirin resistance were significantly correlated with CR. Conclusion. The present study indicated that CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 alleles were not correlated with CR for both Han and Tibetan populations in Qinghai Province, while age, APTT, and aspirin resistance were independent risk factors of CR in this region.</abstract><cop>England</cop><pub>Hindawi</pub><pmid>36325266</pmid><doi>10.1155/2022/1901256</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-6855-4710</orcidid><orcidid>https://orcid.org/0000-0002-5657-421X</orcidid><orcidid>https://orcid.org/0000-0003-4837-2615</orcidid><orcidid>https://orcid.org/0000-0002-5458-6612</orcidid><orcidid>https://orcid.org/0000-0002-3778-1563</orcidid><orcidid>https://orcid.org/0000-0002-0754-8584</orcidid><oa>free_for_read</oa></addata></record>
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source Wiley-Blackwell Open Access Collection; Publicly Available Content Database; PubMed Central
subjects Age
Aged
Aspirin
Blood
Blood platelets
Cardiovascular disease
Cardiovascular diseases
Cerebral Infarction
China
Clopidogrel
Clopidogrel - therapeutic use
Complications
Coronary artery disease
Coronary Disease - drug therapy
Coronary Disease - genetics
Cytochrome P-450 CYP2C19 - genetics
Diabetes mellitus
DNA methylation
Gene polymorphism
Genotype
Genotypes
Geographical distribution
Geographical locations
Heart
Heart diseases
Hemoglobin
Humans
Infarction
Ischemia
Ischemic Stroke
Metabolites
Middle Aged
Minority & ethnic groups
Myocardial infarction
Patients
Polymorphism
Polymorphism, Genetic - genetics
Population studies
Populations
Resistance factors
Risk analysis
Risk factors
Signal transduction
Statistical analysis
Stroke
Thromboplastin
Ticlopidine
title Relationship between CYP2C19 Polymorphism and Clopidogrel Resistance in Patients with Coronary Heart Disease and Ischemic Stroke in China
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