title: APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.
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.
authors.affiliation: For a full list of the authors' affiliations please see the Acknowledgements.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Burkart
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.forename: Jemma B
authors.initials: JB
authors.lastname: Wilk
authors.forename: Firas S
authors.initials: FS
authors.lastname: Ahmed
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Burke
authors.forename: Paul
authors.initials: P
authors.lastname: Enright
authors.forename: Nadia N
authors.initials: NN
authors.lastname: Hansel
authors.forename: Demondes
authors.initials: D
authors.lastname: Haynes
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kaufman
authors.forename: Jun
authors.initials: J
authors.lastname: Kurai
authors.forename: Laura
authors.initials: L
authors.lastname: Loehr
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Yang
authors.initials: Y
authors.lastname: Meng
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Oelsner
authors.forename: Marcy
authors.initials: M
authors.lastname: Petrini
authors.forename: Tess D
authors.initials: TD
authors.lastname: Pottinger
authors.forename: Charles A
authors.initials: CA
authors.lastname: Powell
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Smith
authors.forename: María
authors.initials: M
authors.lastname: Soler Artigas
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: Karol
authors.initials: K
authors.lastname: Watson
authors.forename: Wendy
authors.initials: W
authors.lastname: White
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Young
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D001053:Apolipoproteins / Q000235:genetics*; D000075243:Apolipoproteins M; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D004646:Emphysema / Q000097:blood*; D005260:Female; D005541:Forced Expiratory Volume; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D054834:Lipocalins / Q000235:genetics*; D008168:Lung / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D013147:Spirometry; D014481:United States; D014797:Vital Capacity; D044465:White People
chemical_list: C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D008076:Cholesterol, HDL; D054834:Lipocalins
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