APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema

Kristin M. Burkart, Ani Manichaikul, Jemma B. Wilk, Firas S. Ahmed, Gregory L. Burke, Paul Enright, Nadia Hansel, Demondes Haynes, Susan R. Heckbert, Eric A. Hoffman, Joel D. Kaufman, Jun Kurai, Laura Loehr, Stephanie J. London, Yang Meng, George T. O'Connor, Elizabeth Oelsner, Marcy Petrini, Tess D. Pottinger, Charles A. Powell & 11 others Susan Redline, Jerome I. Rotter, Lewis J. Smith, María Soler Artigas, Martin D. Tobin, Michael Y. Tsai, Karol Watson, Wendy White, Taylor R. Young, Stephen S. Rich, R. Graham Barr

Research output: Contribution to journalArticle

Abstract

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10-6) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10-7). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

Original languageEnglish (US)
Pages (from-to)1003-1017
Number of pages15
JournalEuropean Respiratory Journal
Volume43
Issue number4
DOIs
StatePublished - Apr 1 2014

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Apolipoproteins
Vital Capacity
Emphysema
Forced Expiratory Volume
HDL Cholesterol
African Americans
HDL Lipoproteins
Lung
Chronic Obstructive Pulmonary Disease
Genes
Single Nucleotide Polymorphism
Cardiovascular Diseases
Myeloma Proteins
Pulmonary Emphysema
Biomarkers
Lipids
Gene Expression

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Burkart, K. M., Manichaikul, A., Wilk, J. B., Ahmed, F. S., Burke, G. L., Enright, P., ... Barr, R. G. (2014). APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema. European Respiratory Journal, 43(4), 1003-1017. https://doi.org/10.1183/09031936.00147612

APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema. / Burkart, Kristin M.; Manichaikul, Ani; Wilk, Jemma B.; Ahmed, Firas S.; Burke, Gregory L.; Enright, Paul; Hansel, Nadia; Haynes, Demondes; Heckbert, Susan R.; Hoffman, Eric A.; Kaufman, Joel D.; Kurai, Jun; Loehr, Laura; London, Stephanie J.; Meng, Yang; O'Connor, George T.; Oelsner, Elizabeth; Petrini, Marcy; Pottinger, Tess D.; Powell, Charles A.; Redline, Susan; Rotter, Jerome I.; Smith, Lewis J.; Artigas, María Soler; Tobin, Martin D.; Tsai, Michael Y.; Watson, Karol; White, Wendy; Young, Taylor R.; Rich, Stephen S.; Barr, R. Graham.

In: European Respiratory Journal, Vol. 43, No. 4, 01.04.2014, p. 1003-1017.

Research output: Contribution to journalArticle

Burkart, KM, Manichaikul, A, Wilk, JB, Ahmed, FS, Burke, GL, Enright, P, Hansel, N, Haynes, D, Heckbert, SR, Hoffman, EA, Kaufman, JD, Kurai, J, Loehr, L, London, SJ, Meng, Y, O'Connor, GT, Oelsner, E, Petrini, M, Pottinger, TD, Powell, CA, Redline, S, Rotter, JI, Smith, LJ, Artigas, MS, Tobin, MD, Tsai, MY, Watson, K, White, W, Young, TR, Rich, SS & Barr, RG 2014, 'APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema', European Respiratory Journal, vol. 43, no. 4, pp. 1003-1017. https://doi.org/10.1183/09031936.00147612
Burkart, Kristin M. ; Manichaikul, Ani ; Wilk, Jemma B. ; Ahmed, Firas S. ; Burke, Gregory L. ; Enright, Paul ; Hansel, Nadia ; Haynes, Demondes ; Heckbert, Susan R. ; Hoffman, Eric A. ; Kaufman, Joel D. ; Kurai, Jun ; Loehr, Laura ; London, Stephanie J. ; Meng, Yang ; O'Connor, George T. ; Oelsner, Elizabeth ; Petrini, Marcy ; Pottinger, Tess D. ; Powell, Charles A. ; Redline, Susan ; Rotter, Jerome I. ; Smith, Lewis J. ; Artigas, María Soler ; Tobin, Martin D. ; Tsai, Michael Y. ; Watson, Karol ; White, Wendy ; Young, Taylor R. ; Rich, Stephen S. ; Barr, R. Graham. / APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema. In: European Respiratory Journal. 2014 ; Vol. 43, No. 4. pp. 1003-1017.
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AU - Burkart, Kristin M.

AU - Manichaikul, Ani

AU - Wilk, Jemma B.

AU - Ahmed, Firas S.

AU - Burke, Gregory L.

AU - Enright, Paul

AU - Hansel, Nadia

AU - Haynes, Demondes

AU - Heckbert, Susan R.

AU - Hoffman, Eric A.

AU - Kaufman, Joel D.

AU - Kurai, Jun

AU - Loehr, Laura

AU - London, Stephanie J.

AU - Meng, Yang

AU - O'Connor, George T.

AU - Oelsner, Elizabeth

AU - Petrini, Marcy

AU - Pottinger, Tess D.

AU - Powell, Charles A.

AU - Redline, Susan

AU - Rotter, Jerome I.

AU - Smith, Lewis J.

AU - Artigas, María Soler

AU - Tobin, Martin D.

AU - Tsai, Michael Y.

AU - Watson, Karol

AU - White, Wendy

AU - Young, Taylor R.

AU - Rich, Stephen S.

AU - Barr, R. Graham

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N2 - Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10-6) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10-7). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

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