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Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality
Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients...
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| Published in: | International journal of molecular sciences 2024-10, Vol.25 (19), p.10657 |
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| container_issue | 19 |
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| container_title | International journal of molecular sciences |
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| creator | Monero-Paredes, Mariangeli Santiago, Ednalise Carrasquillo-Carrion, Kelvin Renta, Jessicca Y Rogozin, Igor B Roche-Lima, Abiel Duconge, Jorge |
| description | Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet reactivity unit (PRU), PON1 abundance by Western blotting, and PON1 activity by enzymatic assays were measured.
genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (
> 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL;
= 0.004). PON1 activity among carriers of the most prevalent
haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL;
= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics. |
| doi_str_mv | 10.3390/ijms251910657 |
| format | article |
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genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (
> 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL;
= 0.004). PON1 activity among carriers of the most prevalent
haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL;
= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms251910657</identifier><identifier>PMID: 39408985</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acute coronary syndromes ; Aged ; Aryldialkylphosphatase - genetics ; Aryldialkylphosphatase - metabolism ; Atherosclerosis ; Biomarkers ; Biomarkers - blood ; Blood platelets ; Body mass index ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - drug therapy ; Cardiovascular Diseases - genetics ; Caribbean Hispanics ; Caribbean Region ; Clopidogrel ; Clopidogrel - therapeutic use ; Coronary vessels ; Development and progression ; Dosage and administration ; Drug therapy ; Enzymes ; Female ; Genetic aspects ; Genetic polymorphisms ; Haplotypes ; Health aspects ; Heart attacks ; Hispanic or Latino - genetics ; Humans ; Hypotheses ; Latin Americans ; Male ; Middle Aged ; Patients ; Physiological aspects ; Plasma ; Platelet Aggregation Inhibitors - therapeutic use ; Polymorphism ; Polymorphism, Single Nucleotide ; PON1 ; Proteins ; resistance ; Vein & artery diseases</subject><ispartof>International journal of molecular sciences, 2024-10, Vol.25 (19), p.10657</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c435t-99addc4b5023e3c315f1de83bd4cf11f941b183565b0254060aa8bd11c0ec1bb3</cites><orcidid>0000-0003-2246-6744 ; 0000-0001-7224-2349 ; 0000-0002-5955-3449 ; 0000-0003-0802-4851</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3116670871/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3116670871?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39408985$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Monero-Paredes, Mariangeli</creatorcontrib><creatorcontrib>Santiago, Ednalise</creatorcontrib><creatorcontrib>Carrasquillo-Carrion, Kelvin</creatorcontrib><creatorcontrib>Renta, Jessicca Y</creatorcontrib><creatorcontrib>Rogozin, Igor B</creatorcontrib><creatorcontrib>Roche-Lima, Abiel</creatorcontrib><creatorcontrib>Duconge, Jorge</creatorcontrib><title>Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet reactivity unit (PRU), PON1 abundance by Western blotting, and PON1 activity by enzymatic assays were measured.
genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (
> 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL;
= 0.004). PON1 activity among carriers of the most prevalent
haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL;
= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.</description><subject>Acute coronary syndromes</subject><subject>Aged</subject><subject>Aryldialkylphosphatase - genetics</subject><subject>Aryldialkylphosphatase - metabolism</subject><subject>Atherosclerosis</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Blood platelets</subject><subject>Body mass index</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - drug therapy</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Caribbean Hispanics</subject><subject>Caribbean Region</subject><subject>Clopidogrel</subject><subject>Clopidogrel - therapeutic use</subject><subject>Coronary vessels</subject><subject>Development and progression</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Enzymes</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Heart attacks</subject><subject>Hispanic or Latino - genetics</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Latin Americans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Patients</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Platelet Aggregation Inhibitors - therapeutic use</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>PON1</subject><subject>Proteins</subject><subject>resistance</subject><subject>Vein & artery diseases</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkk1vEzEQhlcIREvgyBVZ4sIlxbP2fnFBaURppUr0UM7W2J5NHTZ2sHcLvfHTcZtSGoR8sGU_fkbvaIriNfAjITr-3q03qaygA15XzZPiEGRZzjmvm6ePzgfFi5TWnJeirLrnxYHoJG-7tjosfl1gxPAzeEw0B4aJIVtitC5cYzLTgJEdu7DB-I0ic_72zWlN6NmpS1v0zrALHB35MbHLSDiSZT_ceMWWQ9g6G1aRhg9soSdv0Rti6C07mbwZXS45uPHmZfGsxyHRq_t9Vnw9-XS5PJ2ff_l8tlycz40U1TjvOrTWSF3lDCSMgKoHS63QVpoeoO8kaGhFVVeal5XkNUdstQUwnAxoLWbF2c5rA67VNrqc6UYFdOruIsSVwjg6M5ACqYnKDo1sKZtEm1uY9SW2fdlgLj8rPu5c20lvyJqcPuKwJ91_8e5KrcK1ApBNA7zNhnf3hhi-T5RGtXHJ0DCgpzAlJQAa3tQ1lxl9-w-6DlPMzbuj6rrhbQN_qRXmBM73IRc2t1K1aKGsQdYdz9TRf6i8LG2cCZ56l-_3Psx3H0wMKUXqH0ICV7fzp_bmL_NvHnfmgf4zcOI3_wLWDQ</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Monero-Paredes, Mariangeli</creator><creator>Santiago, Ednalise</creator><creator>Carrasquillo-Carrion, Kelvin</creator><creator>Renta, Jessicca Y</creator><creator>Rogozin, Igor B</creator><creator>Roche-Lima, Abiel</creator><creator>Duconge, Jorge</creator><general>MDPI AG</general><general>MDPI</general><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2246-6744</orcidid><orcidid>https://orcid.org/0000-0001-7224-2349</orcidid><orcidid>https://orcid.org/0000-0002-5955-3449</orcidid><orcidid>https://orcid.org/0000-0003-0802-4851</orcidid></search><sort><creationdate>20241001</creationdate><title>Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality</title><author>Monero-Paredes, Mariangeli ; Santiago, Ednalise ; Carrasquillo-Carrion, Kelvin ; Renta, Jessicca Y ; Rogozin, Igor B ; Roche-Lima, Abiel ; Duconge, Jorge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-99addc4b5023e3c315f1de83bd4cf11f941b183565b0254060aa8bd11c0ec1bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acute coronary syndromes</topic><topic>Aged</topic><topic>Aryldialkylphosphatase - genetics</topic><topic>Aryldialkylphosphatase - metabolism</topic><topic>Atherosclerosis</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Blood platelets</topic><topic>Body mass index</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - drug therapy</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Caribbean Hispanics</topic><topic>Caribbean Region</topic><topic>Clopidogrel</topic><topic>Clopidogrel - therapeutic use</topic><topic>Coronary vessels</topic><topic>Development and progression</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Enzymes</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genetic polymorphisms</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Heart attacks</topic><topic>Hispanic or Latino - genetics</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Latin Americans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Patients</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Platelet Aggregation Inhibitors - therapeutic use</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>PON1</topic><topic>Proteins</topic><topic>resistance</topic><topic>Vein & artery diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Monero-Paredes, Mariangeli</creatorcontrib><creatorcontrib>Santiago, Ednalise</creatorcontrib><creatorcontrib>Carrasquillo-Carrion, Kelvin</creatorcontrib><creatorcontrib>Renta, Jessicca Y</creatorcontrib><creatorcontrib>Rogozin, Igor B</creatorcontrib><creatorcontrib>Roche-Lima, Abiel</creatorcontrib><creatorcontrib>Duconge, Jorge</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Monero-Paredes, Mariangeli</au><au>Santiago, Ednalise</au><au>Carrasquillo-Carrion, Kelvin</au><au>Renta, Jessicca Y</au><au>Rogozin, Igor B</au><au>Roche-Lima, Abiel</au><au>Duconge, Jorge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2024-10-01</date><risdate>2024</risdate><volume>25</volume><issue>19</issue><spage>10657</spage><pages>10657-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet reactivity unit (PRU), PON1 abundance by Western blotting, and PON1 activity by enzymatic assays were measured.
genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (
> 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL;
= 0.004). PON1 activity among carriers of the most prevalent
haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL;
= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39408985</pmid><doi>10.3390/ijms251910657</doi><orcidid>https://orcid.org/0000-0003-2246-6744</orcidid><orcidid>https://orcid.org/0000-0001-7224-2349</orcidid><orcidid>https://orcid.org/0000-0002-5955-3449</orcidid><orcidid>https://orcid.org/0000-0003-0802-4851</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2024-10, Vol.25 (19), p.10657 |
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| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_14bee29ac48e4063800641b2a8f27a3e |
| source | Access via ProQuest (Open Access); PubMed Central |
| subjects | Acute coronary syndromes Aged Aryldialkylphosphatase - genetics Aryldialkylphosphatase - metabolism Atherosclerosis Biomarkers Biomarkers - blood Blood platelets Body mass index Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - drug therapy Cardiovascular Diseases - genetics Caribbean Hispanics Caribbean Region Clopidogrel Clopidogrel - therapeutic use Coronary vessels Development and progression Dosage and administration Drug therapy Enzymes Female Genetic aspects Genetic polymorphisms Haplotypes Health aspects Heart attacks Hispanic or Latino - genetics Humans Hypotheses Latin Americans Male Middle Aged Patients Physiological aspects Plasma Platelet Aggregation Inhibitors - therapeutic use Polymorphism Polymorphism, Single Nucleotide PON1 Proteins resistance Vein & artery diseases |
| title | Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality |
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