Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.
Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases...
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doaj-f22f154c4fba498b8c748504268fdb822020-11-25T02:25:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10408210.1371/journal.pone.0104082Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.Maria Sabater-LlealAnders MälarstigLasse FolkersenMaría Soler ArtigasDamiano BaldassarreMaryam KavousiPeter AlmgrenFabrizio VegliaGuy BrusselleAlbert HofmanGunnar EngströmOscar H FrancoOlle MelanderGabrielle Paulsson-BerneHugh WatkinsPer ErikssonSteve E HumphriesElena TremoliUlf de FaireMartin D TobinAnders HamstenChronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5 × 10(-4), per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD.http://europepmc.org/articles/PMC4122436?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Sabater-Lleal Anders Mälarstig Lasse Folkersen María Soler Artigas Damiano Baldassarre Maryam Kavousi Peter Almgren Fabrizio Veglia Guy Brusselle Albert Hofman Gunnar Engström Oscar H Franco Olle Melander Gabrielle Paulsson-Berne Hugh Watkins Per Eriksson Steve E Humphries Elena Tremoli Ulf de Faire Martin D Tobin Anders Hamsten |
spellingShingle |
Maria Sabater-Lleal Anders Mälarstig Lasse Folkersen María Soler Artigas Damiano Baldassarre Maryam Kavousi Peter Almgren Fabrizio Veglia Guy Brusselle Albert Hofman Gunnar Engström Oscar H Franco Olle Melander Gabrielle Paulsson-Berne Hugh Watkins Per Eriksson Steve E Humphries Elena Tremoli Ulf de Faire Martin D Tobin Anders Hamsten Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease. PLoS ONE |
author_facet |
Maria Sabater-Lleal Anders Mälarstig Lasse Folkersen María Soler Artigas Damiano Baldassarre Maryam Kavousi Peter Almgren Fabrizio Veglia Guy Brusselle Albert Hofman Gunnar Engström Oscar H Franco Olle Melander Gabrielle Paulsson-Berne Hugh Watkins Per Eriksson Steve E Humphries Elena Tremoli Ulf de Faire Martin D Tobin Anders Hamsten |
author_sort |
Maria Sabater-Lleal |
title |
Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease. |
title_short |
Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease. |
title_full |
Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease. |
title_fullStr |
Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease. |
title_full_unstemmed |
Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease. |
title_sort |
common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5 × 10(-4), per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD. |
url |
http://europepmc.org/articles/PMC4122436?pdf=render |
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