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Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.

Sabater-Lleal, Maria; Mälarstig, Anders; Folkersen, Lasse; Soler Artigas, María; Baldassarre, Damiano; Kavousi, Maryam; Almgren, Peter LU ; Veglia, Fabrizio; Brusselle, Guy and Hofman, Albert, et al. (2014) In PLoS ONE 9(8).
Abstract
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.... (More)
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. (Less)
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@article{4ee4ea9a-e9a4-47b1-ae7f-246cd917e01c,
  abstract     = {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.},
  articleno    = {e104082},
  author       = {Sabater-Lleal, Maria and Mälarstig, Anders and Folkersen, Lasse and Soler Artigas, María and Baldassarre, Damiano and Kavousi, Maryam and Almgren, Peter and Veglia, Fabrizio and Brusselle, Guy and Hofman, Albert and Engström, Gunnar and Franco, Oscar H and Melander, Olle and Paulsson-Berne, Gabrielle and Watkins, Hugh and Eriksson, Per and Humphries, Steve E and Tremoli, Elena and de Faire, Ulf and Tobin, Martin D and Hamsten, Anders},
  issn         = {1932-6203},
  language     = {eng},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0104082},
  volume       = {9},
  year         = {2014},
}