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Combined Polymorphisms in Oxidative Stress Genes Predict Coronary Artery Disease and Oxidative Stress in Coronary Angiography Patients
Summary Oxidative stress has been implicated in all stages of atherosclerosis, but how inherited variations in oxidative stress genes influence the severity of cardiovascular disease is not known. We tested associations between polymorphisms in candidate oxidative stress genes, plasma oxidative stre...
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| Published in: | Annals of human genetics 2012-11, Vol.76 (6), p.435-447 |
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| Main Authors: | , , , , |
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| cites | cdi_FETCH-LOGICAL-c5171-7add6addc826f239ee09fdded42b55da62122a0d46ca658030b29a12939a90683 |
| container_end_page | 447 |
| container_issue | 6 |
| container_start_page | 435 |
| container_title | Annals of human genetics |
| container_volume | 76 |
| creator | Heslop, Claire L. Tebbutt, Scott J. Podder, Mohua Ruan, Jian Hill, John S. |
| description | Summary
Oxidative stress has been implicated in all stages of atherosclerosis, but how inherited variations in oxidative stress genes influence the severity of cardiovascular disease is not known. We tested associations between polymorphisms in candidate oxidative stress genes, plasma oxidative stress biomarkers, and cardiovascular mortality in an angiography cohort.
Single nucleotide polymorphisms (SNPs) across 15 genes were selected by linkage disequilibrium tagging. Genotyping was performed using customized arrayed primer extension micro‐arrays, with automated genotype calling methods. Effects of SNPs and haplotypes on plasma oxidative stress and coronary artery disease (CAD) were estimated using a stochastic estimation maximization algorithm. Proportionate hazards analyses were used to determine effects of single and combined genetic markers on cardiovascular mortality risk, and on the following oxidative stress biomarkers: myeloperoxidase (MPO), nitrotyrosine, oxidized low‐density lipoprotein, and antioxidant capacity.
Oxidative stress gene SNPs associated with CAD were combined into an oxidative stress risk allele score, which predicted disease presence (1.5‐fold risk increase per allele, P < 0.001). Combined risk alleles were also associated with elevated plasma MPO (P < 0.003), an oxidative stress biomarker that predicts cardiovascular mortality.
Genetic markers that represent lifetime oxidative stress burden may implicate specific oxidative stress pathways in the pathogenesis of atherosclerosis, and offer therapeutic opportunities. |
| doi_str_mv | 10.1111/j.1469-1809.2012.00731.x |
| format | article |
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Oxidative stress has been implicated in all stages of atherosclerosis, but how inherited variations in oxidative stress genes influence the severity of cardiovascular disease is not known. We tested associations between polymorphisms in candidate oxidative stress genes, plasma oxidative stress biomarkers, and cardiovascular mortality in an angiography cohort.
Single nucleotide polymorphisms (SNPs) across 15 genes were selected by linkage disequilibrium tagging. Genotyping was performed using customized arrayed primer extension micro‐arrays, with automated genotype calling methods. Effects of SNPs and haplotypes on plasma oxidative stress and coronary artery disease (CAD) were estimated using a stochastic estimation maximization algorithm. Proportionate hazards analyses were used to determine effects of single and combined genetic markers on cardiovascular mortality risk, and on the following oxidative stress biomarkers: myeloperoxidase (MPO), nitrotyrosine, oxidized low‐density lipoprotein, and antioxidant capacity.
Oxidative stress gene SNPs associated with CAD were combined into an oxidative stress risk allele score, which predicted disease presence (1.5‐fold risk increase per allele, P < 0.001). Combined risk alleles were also associated with elevated plasma MPO (P < 0.003), an oxidative stress biomarker that predicts cardiovascular mortality.
Genetic markers that represent lifetime oxidative stress burden may implicate specific oxidative stress pathways in the pathogenesis of atherosclerosis, and offer therapeutic opportunities.</description><identifier>ISSN: 0003-4800</identifier><identifier>EISSN: 1469-1809</identifier><identifier>DOI: 10.1111/j.1469-1809.2012.00731.x</identifier><identifier>PMID: 23003332</identifier><identifier>CODEN: ANHGAA</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Aged ; Algorithms ; Angiography ; Antioxidants ; arrayed primer extension micro-arrays (APEX) ; Arteriosclerosis ; Atherosclerosis ; Biomarkers ; Cardiovascular disease ; Cardiovascular diseases ; Cohort Studies ; combined risk alleles ; Coronary Angiography ; Coronary Artery Disease - diagnosis ; Coronary Artery Disease - genetics ; Coronary Artery Disease - mortality ; Female ; Gene polymorphism ; Genes ; Genetic markers ; Genotype ; Haplotypes ; Heart diseases ; Humans ; Linkage disequilibrium ; Lipoproteins ; Male ; Middle Aged ; Mortality ; nitrotyrosine ; Oxidative stress ; Oxidative Stress - genetics ; oxidative stress genes ; Peroxidase ; plasma myeloperoxidase ; Polymorphism, Single Nucleotide ; Primers ; Prognosis ; Single-nucleotide polymorphism ; Stochasticity</subject><ispartof>Annals of human genetics, 2012-11, Vol.76 (6), p.435-447</ispartof><rights>2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing Ltd/University College London</rights><rights>2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing Ltd/University College London.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5171-7add6addc826f239ee09fdded42b55da62122a0d46ca658030b29a12939a90683</citedby><cites>FETCH-LOGICAL-c5171-7add6addc826f239ee09fdded42b55da62122a0d46ca658030b29a12939a90683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23003332$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heslop, Claire L.</creatorcontrib><creatorcontrib>Tebbutt, Scott J.</creatorcontrib><creatorcontrib>Podder, Mohua</creatorcontrib><creatorcontrib>Ruan, Jian</creatorcontrib><creatorcontrib>Hill, John S.</creatorcontrib><title>Combined Polymorphisms in Oxidative Stress Genes Predict Coronary Artery Disease and Oxidative Stress in Coronary Angiography Patients</title><title>Annals of human genetics</title><addtitle>Ann Hum Genet</addtitle><description>Summary
Oxidative stress has been implicated in all stages of atherosclerosis, but how inherited variations in oxidative stress genes influence the severity of cardiovascular disease is not known. We tested associations between polymorphisms in candidate oxidative stress genes, plasma oxidative stress biomarkers, and cardiovascular mortality in an angiography cohort.
Single nucleotide polymorphisms (SNPs) across 15 genes were selected by linkage disequilibrium tagging. Genotyping was performed using customized arrayed primer extension micro‐arrays, with automated genotype calling methods. Effects of SNPs and haplotypes on plasma oxidative stress and coronary artery disease (CAD) were estimated using a stochastic estimation maximization algorithm. Proportionate hazards analyses were used to determine effects of single and combined genetic markers on cardiovascular mortality risk, and on the following oxidative stress biomarkers: myeloperoxidase (MPO), nitrotyrosine, oxidized low‐density lipoprotein, and antioxidant capacity.
Oxidative stress gene SNPs associated with CAD were combined into an oxidative stress risk allele score, which predicted disease presence (1.5‐fold risk increase per allele, P < 0.001). Combined risk alleles were also associated with elevated plasma MPO (P < 0.003), an oxidative stress biomarker that predicts cardiovascular mortality.
Genetic markers that represent lifetime oxidative stress burden may implicate specific oxidative stress pathways in the pathogenesis of atherosclerosis, and offer therapeutic opportunities.</description><subject>Aged</subject><subject>Algorithms</subject><subject>Angiography</subject><subject>Antioxidants</subject><subject>arrayed primer extension micro-arrays (APEX)</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Biomarkers</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cohort Studies</subject><subject>combined risk alleles</subject><subject>Coronary Angiography</subject><subject>Coronary Artery Disease - diagnosis</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary Artery Disease - mortality</subject><subject>Female</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic markers</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Linkage disequilibrium</subject><subject>Lipoproteins</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>nitrotyrosine</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - genetics</subject><subject>oxidative stress genes</subject><subject>Peroxidase</subject><subject>plasma myeloperoxidase</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Primers</subject><subject>Prognosis</subject><subject>Single-nucleotide polymorphism</subject><subject>Stochasticity</subject><issn>0003-4800</issn><issn>1469-1809</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNkd2O0zAQhS0EYrsLr4AsccNNwthOHEfipspCF1ixlfi7tNx4uuuSxMVO2fYFeG5cuhQJLsCSNZbmO2fkOYRQBjlL5_kqZ4WsM6agzjkwngNUguXbe2RybNwnEwAQWaEATshpjCtIpCrEQ3LCReoIwSfke-P7hRvQ0rnvdr0P6xsX-0jdQK-2zprRfUP6fgwYI53hgJHOA1rXjrTxwQ8m7Og0jJjKuYtoIlIz2L-lye43P1w7fx3M-mZH54nCYYyPyIOl6SI-vqtn5OOrlx-ai-zyava6mV5mbckqllXGWpluq7hcclEjQr20Fm3BF2VpjeSMcwO2kK2RpQIBC14bxmtRmxqkEmfk2cF3HfzXDcZR9y622HVmQL-JmnFRQc3TEv-NMl5yIRnwhD79A135TRjSRzQri0KVqhRVotSBaoOPMeBSr4Pr00Y0A72PVa_0Pj29T0_vY9U_Y9XbJH1yN2Cz6NEehb9yTMCLA3DrOtz9t7GeXszSI8mzg9zFEbdHuQlftKxEVerP72b6k4JGvqmEfit-AMKjv-8</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Heslop, Claire L.</creator><creator>Tebbutt, Scott J.</creator><creator>Podder, Mohua</creator><creator>Ruan, Jian</creator><creator>Hill, John S.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201211</creationdate><title>Combined Polymorphisms in Oxidative Stress Genes Predict Coronary Artery Disease and Oxidative Stress in Coronary Angiography Patients</title><author>Heslop, Claire L. ; Tebbutt, Scott J. ; Podder, Mohua ; Ruan, Jian ; Hill, John S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5171-7add6addc826f239ee09fdded42b55da62122a0d46ca658030b29a12939a90683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Algorithms</topic><topic>Angiography</topic><topic>Antioxidants</topic><topic>arrayed primer extension micro-arrays (APEX)</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Biomarkers</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cohort Studies</topic><topic>combined risk alleles</topic><topic>Coronary Angiography</topic><topic>Coronary Artery Disease - diagnosis</topic><topic>Coronary Artery Disease - genetics</topic><topic>Coronary Artery Disease - mortality</topic><topic>Female</topic><topic>Gene polymorphism</topic><topic>Genes</topic><topic>Genetic markers</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Heart diseases</topic><topic>Humans</topic><topic>Linkage disequilibrium</topic><topic>Lipoproteins</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>nitrotyrosine</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - genetics</topic><topic>oxidative stress genes</topic><topic>Peroxidase</topic><topic>plasma myeloperoxidase</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Primers</topic><topic>Prognosis</topic><topic>Single-nucleotide polymorphism</topic><topic>Stochasticity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heslop, Claire L.</creatorcontrib><creatorcontrib>Tebbutt, Scott J.</creatorcontrib><creatorcontrib>Podder, Mohua</creatorcontrib><creatorcontrib>Ruan, Jian</creatorcontrib><creatorcontrib>Hill, John S.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heslop, Claire L.</au><au>Tebbutt, Scott J.</au><au>Podder, Mohua</au><au>Ruan, Jian</au><au>Hill, John S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined Polymorphisms in Oxidative Stress Genes Predict Coronary Artery Disease and Oxidative Stress in Coronary Angiography Patients</atitle><jtitle>Annals of human genetics</jtitle><addtitle>Ann Hum Genet</addtitle><date>2012-11</date><risdate>2012</risdate><volume>76</volume><issue>6</issue><spage>435</spage><epage>447</epage><pages>435-447</pages><issn>0003-4800</issn><eissn>1469-1809</eissn><coden>ANHGAA</coden><abstract>Summary
Oxidative stress has been implicated in all stages of atherosclerosis, but how inherited variations in oxidative stress genes influence the severity of cardiovascular disease is not known. We tested associations between polymorphisms in candidate oxidative stress genes, plasma oxidative stress biomarkers, and cardiovascular mortality in an angiography cohort.
Single nucleotide polymorphisms (SNPs) across 15 genes were selected by linkage disequilibrium tagging. Genotyping was performed using customized arrayed primer extension micro‐arrays, with automated genotype calling methods. Effects of SNPs and haplotypes on plasma oxidative stress and coronary artery disease (CAD) were estimated using a stochastic estimation maximization algorithm. Proportionate hazards analyses were used to determine effects of single and combined genetic markers on cardiovascular mortality risk, and on the following oxidative stress biomarkers: myeloperoxidase (MPO), nitrotyrosine, oxidized low‐density lipoprotein, and antioxidant capacity.
Oxidative stress gene SNPs associated with CAD were combined into an oxidative stress risk allele score, which predicted disease presence (1.5‐fold risk increase per allele, P < 0.001). Combined risk alleles were also associated with elevated plasma MPO (P < 0.003), an oxidative stress biomarker that predicts cardiovascular mortality.
Genetic markers that represent lifetime oxidative stress burden may implicate specific oxidative stress pathways in the pathogenesis of atherosclerosis, and offer therapeutic opportunities.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>23003332</pmid><doi>10.1111/j.1469-1809.2012.00731.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Annals of human genetics, 2012-11, Vol.76 (6), p.435-447 |
| issn | 0003-4800 1469-1809 |
| language | eng |
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| source | Wiley |
| subjects | Aged Algorithms Angiography Antioxidants arrayed primer extension micro-arrays (APEX) Arteriosclerosis Atherosclerosis Biomarkers Cardiovascular disease Cardiovascular diseases Cohort Studies combined risk alleles Coronary Angiography Coronary Artery Disease - diagnosis Coronary Artery Disease - genetics Coronary Artery Disease - mortality Female Gene polymorphism Genes Genetic markers Genotype Haplotypes Heart diseases Humans Linkage disequilibrium Lipoproteins Male Middle Aged Mortality nitrotyrosine Oxidative stress Oxidative Stress - genetics oxidative stress genes Peroxidase plasma myeloperoxidase Polymorphism, Single Nucleotide Primers Prognosis Single-nucleotide polymorphism Stochasticity |
| title | Combined Polymorphisms in Oxidative Stress Genes Predict Coronary Artery Disease and Oxidative Stress in Coronary Angiography Patients |
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