Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel
The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet acti...
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| Veröffentlicht in: | Molecular biology reports 2019-08, Vol.46 (4), p.4195-4199 |
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| creator | Mirzaev, K. B. Samsonova, K. I. Potapov, P. P. Andreev, D. A. Grishina, E. A. Ryzhikova, K. A. Sychev, D. A. |
| description | The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37–91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)—CC, 4 (4.9%)—CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)—GG, 3 (3.7%)—AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46–26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance. |
| doi_str_mv | 10.1007/s11033-019-04871-y |
| format | Article |
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B. ; Samsonova, K. I. ; Potapov, P. P. ; Andreev, D. A. ; Grishina, E. A. ; Ryzhikova, K. A. ; Sychev, D. A.</creator><creatorcontrib>Mirzaev, K. B. ; Samsonova, K. I. ; Potapov, P. P. ; Andreev, D. A. ; Grishina, E. A. ; Ryzhikova, K. A. ; Sychev, D. A.</creatorcontrib><description>The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37–91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)—CC, 4 (4.9%)—CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)—GG, 3 (3.7%)—AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46–26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-019-04871-y</identifier><identifier>PMID: 31102151</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Acute Coronary Syndrome - drug therapy ; Acute Coronary Syndrome - genetics ; Acute coronary syndromes ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Animal Anatomy ; Animal Biochemistry ; Biomarkers, Pharmacological ; Biomedical and Life Sciences ; Blood Platelets - metabolism ; Clopidogrel ; Clopidogrel - pharmacology ; Coronary Artery Disease - genetics ; Cortisol ; CYP3A protein ; Cytochrome P-450 CYP3A - genetics ; Cytochrome P-450 CYP3A - metabolism ; Female ; Gene frequency ; Gene Frequency - genetics ; Gene polymorphism ; Genotype ; Genotyping ; High-performance liquid chromatography ; Histology ; Humans ; Isoenzymes ; Life Sciences ; Male ; Middle Aged ; Morphology ; Original Article ; Phenotype ; Phenotyping ; Platelet aggregation ; Platelet Aggregation - drug effects ; Platelet Aggregation - genetics ; Platelet Aggregation Inhibitors - metabolism ; Platelet Aggregation Inhibitors - pharmacology ; Polymorphism, Genetic - genetics ; Statistical analysis</subject><ispartof>Molecular biology reports, 2019-08, Vol.46 (4), p.4195-4199</ispartof><rights>Springer Nature B.V. 2019</rights><rights>Molecular Biology Reports is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-f2c7469c90cb791efc4372f88936d4649172af99bee1fdf4fb3a5ac731c91dbc3</citedby><cites>FETCH-LOGICAL-c375t-f2c7469c90cb791efc4372f88936d4649172af99bee1fdf4fb3a5ac731c91dbc3</cites><orcidid>0000-0002-0174-2765 ; 0000-0003-3505-8520 ; 0000-0002-9307-4994 ; 0000-0002-4496-3680 ; 0000-0002-0276-7374 ; 0000-0002-5621-8266</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-019-04871-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-019-04871-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31102151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mirzaev, K. B.</creatorcontrib><creatorcontrib>Samsonova, K. I.</creatorcontrib><creatorcontrib>Potapov, P. P.</creatorcontrib><creatorcontrib>Andreev, D. A.</creatorcontrib><creatorcontrib>Grishina, E. A.</creatorcontrib><creatorcontrib>Ryzhikova, K. A.</creatorcontrib><creatorcontrib>Sychev, D. A.</creatorcontrib><title>Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><addtitle>Mol Biol Rep</addtitle><description>The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37–91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)—CC, 4 (4.9%)—CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)—GG, 3 (3.7%)—AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46–26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.</description><subject>Acute Coronary Syndrome - drug therapy</subject><subject>Acute Coronary Syndrome - genetics</subject><subject>Acute coronary syndromes</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>Biomarkers, Pharmacological</subject><subject>Biomedical and Life Sciences</subject><subject>Blood Platelets - metabolism</subject><subject>Clopidogrel</subject><subject>Clopidogrel - pharmacology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Cortisol</subject><subject>CYP3A protein</subject><subject>Cytochrome P-450 CYP3A - genetics</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>Female</subject><subject>Gene frequency</subject><subject>Gene Frequency - genetics</subject><subject>Gene polymorphism</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>High-performance liquid chromatography</subject><subject>Histology</subject><subject>Humans</subject><subject>Isoenzymes</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Morphology</subject><subject>Original Article</subject><subject>Phenotype</subject><subject>Phenotyping</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation - genetics</subject><subject>Platelet Aggregation Inhibitors - metabolism</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Statistical analysis</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kE9LwzAYh4Mobv75Ah6k4MVLNW-SNo03GToFQQ96EISYpsmsdE1tUmTf3rhNBx48vYQ8v1_ePAgdAT4DjPm5B8CUphhEilnBIV1soTFknKZM8GIbjTHFkLIigxHa8_4dY8yAZ7toRGOSQAZj9Do1rQuLrm5niWqrpHvbnCfPD_SSvSxHdpG0LlHeO12rULs2-azDW4yEumtUMI0JibHW6JA4m-jGdXXlZr1pDtCOVY03h-u5j56urx4nN-nd_fR2cnmXasqzkFqiOcuFFliXXICxmlFObFEImlcsZwI4UVaI0hiwlWW2pCpTmlPQAqpS0310uurtevcxGB_kvPbaNI1qjRu8JISS-H1MSURP_qDvbujbuF2kSJ4TXpA8UmRF6d553xsru76eq34hActv_3LlX0b_culfLmLoeF09lHNT_UZ-hEeArgAfr9qZ6Tdv_1P7BU2nkJY</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Mirzaev, K. 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B.</au><au>Samsonova, K. I.</au><au>Potapov, P. P.</au><au>Andreev, D. A.</au><au>Grishina, E. A.</au><au>Ryzhikova, K. A.</au><au>Sychev, D. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel</atitle><jtitle>Molecular biology reports</jtitle><stitle>Mol Biol Rep</stitle><addtitle>Mol Biol Rep</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>46</volume><issue>4</issue><spage>4195</spage><epage>4199</epage><pages>4195-4199</pages><issn>0301-4851</issn><eissn>1573-4978</eissn><abstract>The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37–91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)—CC, 4 (4.9%)—CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)—GG, 3 (3.7%)—AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46–26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>31102151</pmid><doi>10.1007/s11033-019-04871-y</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-0174-2765</orcidid><orcidid>https://orcid.org/0000-0003-3505-8520</orcidid><orcidid>https://orcid.org/0000-0002-9307-4994</orcidid><orcidid>https://orcid.org/0000-0002-4496-3680</orcidid><orcidid>https://orcid.org/0000-0002-0276-7374</orcidid><orcidid>https://orcid.org/0000-0002-5621-8266</orcidid></addata></record> |
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| subjects | Acute Coronary Syndrome - drug therapy Acute Coronary Syndrome - genetics Acute coronary syndromes Adult Aged Aged, 80 and over Alleles Animal Anatomy Animal Biochemistry Biomarkers, Pharmacological Biomedical and Life Sciences Blood Platelets - metabolism Clopidogrel Clopidogrel - pharmacology Coronary Artery Disease - genetics Cortisol CYP3A protein Cytochrome P-450 CYP3A - genetics Cytochrome P-450 CYP3A - metabolism Female Gene frequency Gene Frequency - genetics Gene polymorphism Genotype Genotyping High-performance liquid chromatography Histology Humans Isoenzymes Life Sciences Male Middle Aged Morphology Original Article Phenotype Phenotyping Platelet aggregation Platelet Aggregation - drug effects Platelet Aggregation - genetics Platelet Aggregation Inhibitors - metabolism Platelet Aggregation Inhibitors - pharmacology Polymorphism, Genetic - genetics Statistical analysis |
| title | Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel |
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