rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography
Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with th...
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| Veröffentlicht in: | Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2021-05, Vol.31 (5), p.1542-1547 |
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| creator | Noto, Davide Cefalù, Angelo B. Martinelli, Nicola Giammanco, Antonina Spina, Rossella Barbagallo, Carlo M. Caruso, Marco Novo, Salvatore Sarullo, Filippo Pernice, Vincenzo Brucato, Federica Ingrassia, Valeria Fayer, Francesca Altieri, Grazia I. Scrimali, Chiara Misiano, Gabriella Olivieri, Oliviero Girelli, Domenico Averna, Maurizio R. |
| description | Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients.
The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG.
The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04–1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04–1.96) and 1.39 (1.22–1.58) respectively].
rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.
•2429 patients subjected to CAG were genotyped for the rs629301 polymorphism.•Critical coronary stenosis was defined as an occlusion >50% of the artery lumen.•Lipids, apolipoproteins and Lp(a) were assayed in the cohort.•The T/T risk genotype was associated with higher levels of lipids, and apolipoproteins.•The independent T/T coronary risk (+43%) equaled the risk of being 10 years older (+39%). |
| doi_str_mv | 10.1016/j.numecd.2021.01.018 |
| format | Article |
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The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG.
The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04–1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04–1.96) and 1.39 (1.22–1.58) respectively].
rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.
•2429 patients subjected to CAG were genotyped for the rs629301 polymorphism.•Critical coronary stenosis was defined as an occlusion >50% of the artery lumen.•Lipids, apolipoproteins and Lp(a) were assayed in the cohort.•The T/T risk genotype was associated with higher levels of lipids, and apolipoproteins.•The independent T/T coronary risk (+43%) equaled the risk of being 10 years older (+39%).</description><identifier>ISSN: 0939-4753</identifier><identifier>EISSN: 1590-3729</identifier><identifier>DOI: 10.1016/j.numecd.2021.01.018</identifier><identifier>PMID: 33810964</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>alleles ; angiography ; Apolipoproteins ; blood ; Coronary artery disease ; Gene polymorphism ; genotype ; high density lipoprotein cholesterol ; Italy ; Lipids ; metabolism ; multigene family ; nutrition ; regression analysis ; risk ; Sortilin</subject><ispartof>Nutrition, metabolism, and cardiovascular diseases, 2021-05, Vol.31 (5), p.1542-1547</ispartof><rights>2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University</rights><rights>Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-82bc2bb49651f7cf8fcd34693d00310b0c281557acd8547cfc54bca52548eb153</citedby><cites>FETCH-LOGICAL-c441t-82bc2bb49651f7cf8fcd34693d00310b0c281557acd8547cfc54bca52548eb153</cites><orcidid>0000-0002-5346-2829 ; 0000-0003-4561-8931 ; 0000-0002-3088-3049</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0939475321000387$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33810964$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noto, Davide</creatorcontrib><creatorcontrib>Cefalù, Angelo B.</creatorcontrib><creatorcontrib>Martinelli, Nicola</creatorcontrib><creatorcontrib>Giammanco, Antonina</creatorcontrib><creatorcontrib>Spina, Rossella</creatorcontrib><creatorcontrib>Barbagallo, Carlo M.</creatorcontrib><creatorcontrib>Caruso, Marco</creatorcontrib><creatorcontrib>Novo, Salvatore</creatorcontrib><creatorcontrib>Sarullo, Filippo</creatorcontrib><creatorcontrib>Pernice, Vincenzo</creatorcontrib><creatorcontrib>Brucato, Federica</creatorcontrib><creatorcontrib>Ingrassia, Valeria</creatorcontrib><creatorcontrib>Fayer, Francesca</creatorcontrib><creatorcontrib>Altieri, Grazia I.</creatorcontrib><creatorcontrib>Scrimali, Chiara</creatorcontrib><creatorcontrib>Misiano, Gabriella</creatorcontrib><creatorcontrib>Olivieri, Oliviero</creatorcontrib><creatorcontrib>Girelli, Domenico</creatorcontrib><creatorcontrib>Averna, Maurizio R.</creatorcontrib><title>rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography</title><title>Nutrition, metabolism, and cardiovascular diseases</title><addtitle>Nutr Metab Cardiovasc Dis</addtitle><description>Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients.
The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG.
The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04–1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04–1.96) and 1.39 (1.22–1.58) respectively].
rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.
•2429 patients subjected to CAG were genotyped for the rs629301 polymorphism.•Critical coronary stenosis was defined as an occlusion >50% of the artery lumen.•Lipids, apolipoproteins and Lp(a) were assayed in the cohort.•The T/T risk genotype was associated with higher levels of lipids, and apolipoproteins.•The independent T/T coronary risk (+43%) equaled the risk of being 10 years older (+39%).</description><subject>alleles</subject><subject>angiography</subject><subject>Apolipoproteins</subject><subject>blood</subject><subject>Coronary artery disease</subject><subject>Gene polymorphism</subject><subject>genotype</subject><subject>high density lipoprotein cholesterol</subject><subject>Italy</subject><subject>Lipids</subject><subject>metabolism</subject><subject>multigene family</subject><subject>nutrition</subject><subject>regression analysis</subject><subject>risk</subject><subject>Sortilin</subject><issn>0939-4753</issn><issn>1590-3729</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqNkU9r3DAQxUVJabZpv0EIOubirf7a0iVQljQpLATS9ixkeZxoY1uOZAf87SuzSY6l8GAuv5nHm4fQOSVbSmj57bAd5h5cs2WE0S1ZpT6gDZWaFLxi-gRtiOa6EJXkp-hzSgdCeEW4-IROOVeU6FJs0BxTyTQnFO-u97_uGR5Dt_Qhjo8-9diFoYWYsMUTDMUCNmJ4nv2L7WCYcPTpCYcWu-gn72yHU6ZC8plPCbIaXC_5RgyDjQu2w4MPD9GOj8sX9LG1XYKvr_MM_flx_Xt3W-zvbn7uvu8LJwSdCsVqx-pa6FLStnKtal3DRal5k6NQUhPHFJWysq5RUmTASVE7K5kUCmoq-Rm6PN4dY3ieIU2m98lB19kBwpwMk0wwprUm_4ESJatSVysqjqiLIaUIrRmj73NEQ4lZuzEHc-zGrN0YskrltYtXh7nuoXlfeisjA1dHAPJLXjxEk5yHwUHjI7jJNMH_2-Ev41miAw</recordid><startdate>20210506</startdate><enddate>20210506</enddate><creator>Noto, Davide</creator><creator>Cefalù, Angelo B.</creator><creator>Martinelli, Nicola</creator><creator>Giammanco, Antonina</creator><creator>Spina, Rossella</creator><creator>Barbagallo, Carlo M.</creator><creator>Caruso, Marco</creator><creator>Novo, Salvatore</creator><creator>Sarullo, Filippo</creator><creator>Pernice, Vincenzo</creator><creator>Brucato, Federica</creator><creator>Ingrassia, Valeria</creator><creator>Fayer, Francesca</creator><creator>Altieri, Grazia I.</creator><creator>Scrimali, Chiara</creator><creator>Misiano, Gabriella</creator><creator>Olivieri, Oliviero</creator><creator>Girelli, Domenico</creator><creator>Averna, Maurizio R.</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-5346-2829</orcidid><orcidid>https://orcid.org/0000-0003-4561-8931</orcidid><orcidid>https://orcid.org/0000-0002-3088-3049</orcidid></search><sort><creationdate>20210506</creationdate><title>rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography</title><author>Noto, Davide ; Cefalù, Angelo B. ; Martinelli, Nicola ; Giammanco, Antonina ; Spina, Rossella ; Barbagallo, Carlo M. ; Caruso, Marco ; Novo, Salvatore ; Sarullo, Filippo ; Pernice, Vincenzo ; Brucato, Federica ; Ingrassia, Valeria ; Fayer, Francesca ; Altieri, Grazia I. ; Scrimali, Chiara ; Misiano, Gabriella ; Olivieri, Oliviero ; Girelli, Domenico ; Averna, Maurizio R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-82bc2bb49651f7cf8fcd34693d00310b0c281557acd8547cfc54bca52548eb153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>alleles</topic><topic>angiography</topic><topic>Apolipoproteins</topic><topic>blood</topic><topic>Coronary artery disease</topic><topic>Gene polymorphism</topic><topic>genotype</topic><topic>high density lipoprotein cholesterol</topic><topic>Italy</topic><topic>Lipids</topic><topic>metabolism</topic><topic>multigene family</topic><topic>nutrition</topic><topic>regression analysis</topic><topic>risk</topic><topic>Sortilin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Noto, Davide</creatorcontrib><creatorcontrib>Cefalù, Angelo B.</creatorcontrib><creatorcontrib>Martinelli, Nicola</creatorcontrib><creatorcontrib>Giammanco, Antonina</creatorcontrib><creatorcontrib>Spina, Rossella</creatorcontrib><creatorcontrib>Barbagallo, Carlo M.</creatorcontrib><creatorcontrib>Caruso, Marco</creatorcontrib><creatorcontrib>Novo, Salvatore</creatorcontrib><creatorcontrib>Sarullo, Filippo</creatorcontrib><creatorcontrib>Pernice, Vincenzo</creatorcontrib><creatorcontrib>Brucato, Federica</creatorcontrib><creatorcontrib>Ingrassia, Valeria</creatorcontrib><creatorcontrib>Fayer, Francesca</creatorcontrib><creatorcontrib>Altieri, Grazia I.</creatorcontrib><creatorcontrib>Scrimali, Chiara</creatorcontrib><creatorcontrib>Misiano, Gabriella</creatorcontrib><creatorcontrib>Olivieri, Oliviero</creatorcontrib><creatorcontrib>Girelli, Domenico</creatorcontrib><creatorcontrib>Averna, Maurizio R.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Nutrition, metabolism, and cardiovascular diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noto, Davide</au><au>Cefalù, Angelo B.</au><au>Martinelli, Nicola</au><au>Giammanco, Antonina</au><au>Spina, Rossella</au><au>Barbagallo, Carlo M.</au><au>Caruso, Marco</au><au>Novo, Salvatore</au><au>Sarullo, Filippo</au><au>Pernice, Vincenzo</au><au>Brucato, Federica</au><au>Ingrassia, Valeria</au><au>Fayer, Francesca</au><au>Altieri, Grazia I.</au><au>Scrimali, Chiara</au><au>Misiano, Gabriella</au><au>Olivieri, Oliviero</au><au>Girelli, Domenico</au><au>Averna, Maurizio R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography</atitle><jtitle>Nutrition, metabolism, and cardiovascular diseases</jtitle><addtitle>Nutr Metab Cardiovasc Dis</addtitle><date>2021-05-06</date><risdate>2021</risdate><volume>31</volume><issue>5</issue><spage>1542</spage><epage>1547</epage><pages>1542-1547</pages><issn>0939-4753</issn><eissn>1590-3729</eissn><abstract>Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients.
The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG.
The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04–1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04–1.96) and 1.39 (1.22–1.58) respectively].
rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.
•2429 patients subjected to CAG were genotyped for the rs629301 polymorphism.•Critical coronary stenosis was defined as an occlusion >50% of the artery lumen.•Lipids, apolipoproteins and Lp(a) were assayed in the cohort.•The T/T risk genotype was associated with higher levels of lipids, and apolipoproteins.•The independent T/T coronary risk (+43%) equaled the risk of being 10 years older (+39%).</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33810964</pmid><doi>10.1016/j.numecd.2021.01.018</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-5346-2829</orcidid><orcidid>https://orcid.org/0000-0003-4561-8931</orcidid><orcidid>https://orcid.org/0000-0002-3088-3049</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | alleles angiography Apolipoproteins blood Coronary artery disease Gene polymorphism genotype high density lipoprotein cholesterol Italy Lipids metabolism multigene family nutrition regression analysis risk Sortilin |
| title | rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography |
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