Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients
Via sequencing the genes of apelin/angiotensin receptor-like 1 (apelin/APJ) pathway, we have recently identified and validated four common polymorphisms (rs3761581, rs56204867, rs7119375, and rs10501367) implicated in the development of hypertension. Extending these findings, we, in Chinese hyperten...
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| description | Via sequencing the genes of apelin/angiotensin receptor-like 1 (apelin/APJ) pathway, we have recently identified and validated four common polymorphisms (rs3761581, rs56204867, rs7119375, and rs10501367) implicated in the development of hypertension. Extending these findings, we, in Chinese hypertensive patients, sought to investigate the association of these four polymorphisms and one additional promising candidate (rs9943582) from this pathway with the risk of developing coronary artery disease (CAD).
Genotypes were obtained from 994 sporadic CAD patients and 708 age- and sex-matched controls. All participants were hypertensives and angiographically-confirmed. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares. Genotype distributions of five examined polymorphisms satisfied Hardy-Weinberg equilibrium in controls of both genders. Single-locus analyses exhibited no significant differences in the genotype/allele frequencies of examined polymorphisms between CAD patients and controls (P>0.05), even after controlling traditional cardiovascular confounders. In haplotype analyses, low-penetrance haplotype G-A (in order of rs56204867 and rs3761581 from apelin gene) was significantly overrepresented in controls (1.73%) relative to in CAD patients (0.4%) in males (P = 0.047). Further interaction analyses suggested an overall best MDR model including rs3761581 in males (P = 0.0408) and including rs7119375 and rs9943582 in females (P |
| doi_str_mv | 10.1371/journal.pone.0051123 |
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Genotypes were obtained from 994 sporadic CAD patients and 708 age- and sex-matched controls. All participants were hypertensives and angiographically-confirmed. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares. Genotype distributions of five examined polymorphisms satisfied Hardy-Weinberg equilibrium in controls of both genders. Single-locus analyses exhibited no significant differences in the genotype/allele frequencies of examined polymorphisms between CAD patients and controls (P>0.05), even after controlling traditional cardiovascular confounders. In haplotype analyses, low-penetrance haplotype G-A (in order of rs56204867 and rs3761581 from apelin gene) was significantly overrepresented in controls (1.73%) relative to in CAD patients (0.4%) in males (P = 0.047). Further interaction analyses suggested an overall best MDR model including rs3761581 in males (P = 0.0408) and including rs7119375 and rs9943582 in females (P<0.0001), which were further substantiated in the classical logistical regression model.
Our findings demonstrated a contributive role of low-penetrance haplotype in apelin gene on CAD in males, and more importantly, interactive effects of genetic defects in apelin/APJ pathway might confer a potential risk in Chinese hypertensive patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0051123</identifier><identifier>PMID: 23226564</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Angiotensin ; Apelin ; Apelin Receptors ; Asian Continental Ancestry Group - genetics ; Binding sites ; Biology ; Biomarkers - metabolism ; Cardiology ; Cardiovascular disease ; Case-Control Studies ; China ; Cholesterol ; Coronary artery ; Coronary artery disease ; Coronary Artery Disease - complications ; Coronary Artery Disease - genetics ; Coronary heart disease ; Coronary vessels ; Data processing ; Defects ; Development and progression ; Epistasis, Genetic ; Fasting ; Female ; Females ; Gender ; Gene frequency ; Gene Frequency - genetics ; Gene sequencing ; Genes ; Genetic aspects ; Genetic Association Studies ; Genetic Loci - genetics ; Genetic Predisposition to Disease ; Genome, Human - genetics ; Genomes ; Genomics ; Genotypes ; Haplotypes ; Haplotypes - genetics ; Health risks ; Heart diseases ; Hospitals ; Humans ; Hypertension ; Hypertension - complications ; Hypertension - genetics ; Hypotheses ; Hypothesis testing ; Intercellular Signaling Peptides and Proteins - genetics ; Laboratories ; Ligands ; Male ; Males ; Medical imaging ; Medical research ; Medicine ; Middle Aged ; Multifactor Dimensionality Reduction ; Patients ; Polymorphism, Single Nucleotide - genetics ; Receptors, G-Protein-Coupled - genetics ; Regression analysis ; Regression models ; Signal Transduction - genetics ; Studies ; Type 2 diabetes</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e51123-e51123</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Jin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Jin et al 2012 Jin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1fd87d3c2ff972f7dcf2daa4a95ba9c06c7d6a199d94b4220fd0c2994e6df8043</citedby><cites>FETCH-LOGICAL-c692t-1fd87d3c2ff972f7dcf2daa4a95ba9c06c7d6a199d94b4220fd0c2994e6df8043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513301/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513301/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23226564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Novelli, Giuseppe</contributor><creatorcontrib>Jin, Wei</creatorcontrib><creatorcontrib>Su, Xiuxiu</creatorcontrib><creatorcontrib>Xu, Min</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Shi, Jingyi</creatorcontrib><creatorcontrib>Lu, Lin</creatorcontrib><creatorcontrib>Niu, Wenquan</creatorcontrib><title>Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Via sequencing the genes of apelin/angiotensin receptor-like 1 (apelin/APJ) pathway, we have recently identified and validated four common polymorphisms (rs3761581, rs56204867, rs7119375, and rs10501367) implicated in the development of hypertension. Extending these findings, we, in Chinese hypertensive patients, sought to investigate the association of these four polymorphisms and one additional promising candidate (rs9943582) from this pathway with the risk of developing coronary artery disease (CAD).
Genotypes were obtained from 994 sporadic CAD patients and 708 age- and sex-matched controls. All participants were hypertensives and angiographically-confirmed. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares. Genotype distributions of five examined polymorphisms satisfied Hardy-Weinberg equilibrium in controls of both genders. Single-locus analyses exhibited no significant differences in the genotype/allele frequencies of examined polymorphisms between CAD patients and controls (P>0.05), even after controlling traditional cardiovascular confounders. In haplotype analyses, low-penetrance haplotype G-A (in order of rs56204867 and rs3761581 from apelin gene) was significantly overrepresented in controls (1.73%) relative to in CAD patients (0.4%) in males (P = 0.047). Further interaction analyses suggested an overall best MDR model including rs3761581 in males (P = 0.0408) and including rs7119375 and rs9943582 in females (P<0.0001), which were further substantiated in the classical logistical regression model.
Our findings demonstrated a contributive role of low-penetrance haplotype in apelin gene on CAD in males, and more importantly, interactive effects of genetic defects in apelin/APJ pathway might confer a potential risk in Chinese hypertensive patients.</description><subject>Analysis</subject><subject>Angiotensin</subject><subject>Apelin</subject><subject>Apelin Receptors</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Binding sites</subject><subject>Biology</subject><subject>Biomarkers - metabolism</subject><subject>Cardiology</subject><subject>Cardiovascular disease</subject><subject>Case-Control Studies</subject><subject>China</subject><subject>Cholesterol</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - complications</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary heart disease</subject><subject>Coronary vessels</subject><subject>Data processing</subject><subject>Defects</subject><subject>Development and progression</subject><subject>Epistasis, Genetic</subject><subject>Fasting</subject><subject>Female</subject><subject>Females</subject><subject>Gender</subject><subject>Gene frequency</subject><subject>Gene Frequency - genetics</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies</subject><subject>Genetic Loci - genetics</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome, Human - genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotypes</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Health risks</subject><subject>Heart diseases</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - complications</subject><subject>Hypertension - genetics</subject><subject>Hypotheses</subject><subject>Hypothesis testing</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Laboratories</subject><subject>Ligands</subject><subject>Male</subject><subject>Males</subject><subject>Medical imaging</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Multifactor Dimensionality Reduction</subject><subject>Patients</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Signal Transduction - genetics</subject><subject>Studies</subject><subject>Type 2 diabetes</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</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><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggiISG42K1Pm6xvkFYrDosqFXG6tSY-bLxK7DROWvYleGYcNq02qBcoF4nH3_-PZ-JJkucYzTHN8fnO962Dat54p-cILTAm9EFyijkls4wg-vDo-yR5EsIuQnSZZY-TE0IJyRYZO01-b1ynW5CdvdYphOClhc56l3qTmiEmwSmroNNp46t97dumtKEOqXXpqtGVdeerL5_TBrryBvbpje3KVPrWO2j3KbTRe58qGzSEaF97t03XpXU6rsp9o-O-C0OWqLfadeFp8shAFfSz8X2W_Pjw_vv60-zi8uNmvbqYyYyTboaNWuaKSmIMz4nJlTREATDgiwK4RJnMVQaYc8VZwQhBRiFJOGc6U2aJGD1LXh58m8oHMbYyCExJlrMlxzgSmwOhPOxE09o6ViQ8WPE34NutiOVZWWmRFxwVGoqlgYIxKApSgGKQq0IuCsOy6PVuzNYXtVYyVtpCNTGd7jhbiq2_FnSBKUXDYd6MBq2_6nXoRG2D1FUFTvs-npvQfIEZQkOuV_-g91c3UluIBVhnfMwrB1OxYnmOOGJk6NL8Hio-StdWxntnbIxPBG8ngsh0-le3hT4Esfn29f_Zy59T9vURW2qoujL4qh9uapiC7ADK1ofQanPXZIzEMDa33RDD2IhxbKLsxfEPuhPdzgn9Ax4lF0c</recordid><startdate>20121203</startdate><enddate>20121203</enddate><creator>Jin, Wei</creator><creator>Su, Xiuxiu</creator><creator>Xu, Min</creator><creator>Liu, Yan</creator><creator>Shi, Jingyi</creator><creator>Lu, Lin</creator><creator>Niu, Wenquan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121203</creationdate><title>Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients</title><author>Jin, Wei ; Su, Xiuxiu ; Xu, Min ; Liu, Yan ; Shi, Jingyi ; Lu, Lin ; Niu, Wenquan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1fd87d3c2ff972f7dcf2daa4a95ba9c06c7d6a199d94b4220fd0c2994e6df8043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Analysis</topic><topic>Angiotensin</topic><topic>Apelin</topic><topic>Apelin Receptors</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Binding sites</topic><topic>Biology</topic><topic>Biomarkers - metabolism</topic><topic>Cardiology</topic><topic>Cardiovascular disease</topic><topic>Case-Control Studies</topic><topic>China</topic><topic>Cholesterol</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - complications</topic><topic>Coronary Artery Disease - genetics</topic><topic>Coronary heart disease</topic><topic>Coronary vessels</topic><topic>Data processing</topic><topic>Defects</topic><topic>Development and progression</topic><topic>Epistasis, Genetic</topic><topic>Fasting</topic><topic>Female</topic><topic>Females</topic><topic>Gender</topic><topic>Gene frequency</topic><topic>Gene Frequency - genetics</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies</topic><topic>Genetic Loci - genetics</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome, Human - genetics</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotypes</topic><topic>Haplotypes</topic><topic>Haplotypes - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Wei</au><au>Su, Xiuxiu</au><au>Xu, Min</au><au>Liu, Yan</au><au>Shi, Jingyi</au><au>Lu, Lin</au><au>Niu, Wenquan</au><au>Novelli, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-03</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e51123</spage><epage>e51123</epage><pages>e51123-e51123</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Via sequencing the genes of apelin/angiotensin receptor-like 1 (apelin/APJ) pathway, we have recently identified and validated four common polymorphisms (rs3761581, rs56204867, rs7119375, and rs10501367) implicated in the development of hypertension. Extending these findings, we, in Chinese hypertensive patients, sought to investigate the association of these four polymorphisms and one additional promising candidate (rs9943582) from this pathway with the risk of developing coronary artery disease (CAD).
Genotypes were obtained from 994 sporadic CAD patients and 708 age- and sex-matched controls. All participants were hypertensives and angiographically-confirmed. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares. Genotype distributions of five examined polymorphisms satisfied Hardy-Weinberg equilibrium in controls of both genders. Single-locus analyses exhibited no significant differences in the genotype/allele frequencies of examined polymorphisms between CAD patients and controls (P>0.05), even after controlling traditional cardiovascular confounders. In haplotype analyses, low-penetrance haplotype G-A (in order of rs56204867 and rs3761581 from apelin gene) was significantly overrepresented in controls (1.73%) relative to in CAD patients (0.4%) in males (P = 0.047). Further interaction analyses suggested an overall best MDR model including rs3761581 in males (P = 0.0408) and including rs7119375 and rs9943582 in females (P<0.0001), which were further substantiated in the classical logistical regression model.
Our findings demonstrated a contributive role of low-penetrance haplotype in apelin gene on CAD in males, and more importantly, interactive effects of genetic defects in apelin/APJ pathway might confer a potential risk in Chinese hypertensive patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23226564</pmid><doi>10.1371/journal.pone.0051123</doi><tpages>e51123</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-12, Vol.7 (12), p.e51123-e51123 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1326748911 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Angiotensin Apelin Apelin Receptors Asian Continental Ancestry Group - genetics Binding sites Biology Biomarkers - metabolism Cardiology Cardiovascular disease Case-Control Studies China Cholesterol Coronary artery Coronary artery disease Coronary Artery Disease - complications Coronary Artery Disease - genetics Coronary heart disease Coronary vessels Data processing Defects Development and progression Epistasis, Genetic Fasting Female Females Gender Gene frequency Gene Frequency - genetics Gene sequencing Genes Genetic aspects Genetic Association Studies Genetic Loci - genetics Genetic Predisposition to Disease Genome, Human - genetics Genomes Genomics Genotypes Haplotypes Haplotypes - genetics Health risks Heart diseases Hospitals Humans Hypertension Hypertension - complications Hypertension - genetics Hypotheses Hypothesis testing Intercellular Signaling Peptides and Proteins - genetics Laboratories Ligands Male Males Medical imaging Medical research Medicine Middle Aged Multifactor Dimensionality Reduction Patients Polymorphism, Single Nucleotide - genetics Receptors, G-Protein-Coupled - genetics Regression analysis Regression models Signal Transduction - genetics Studies Type 2 diabetes |
| title | Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T14%3A13%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interactive%20association%20of%20five%20candidate%20polymorphisms%20in%20Apelin/APJ%20pathway%20with%20coronary%20artery%20disease%20among%20Chinese%20hypertensive%20patients&rft.jtitle=PloS%20one&rft.au=Jin,%20Wei&rft.date=2012-12-03&rft.volume=7&rft.issue=12&rft.spage=e51123&rft.epage=e51123&rft.pages=e51123-e51123&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0051123&rft_dat=%3Cgale_plos_%3EA477090424%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326748911&rft_id=info:pmid/23226564&rft_galeid=A477090424&rft_doaj_id=oai_doaj_org_article_7b90beab8fab44abb2bad4a7dbc5bf46&rfr_iscdi=true |