title: Surfactant protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage.
abstract: Variation in surfactant protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The association between serum SP-D (sSP-D) and expiratory lung function was assessed in a cross-sectional design in a Danish twin population (n = 1,512, 18-72 yr old). The adjusted heritability estimates for expiratory lung function, associations between SP-D gene (SFTPD) single-nucleotide polymorphisms or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 s and forced vital capacity in the presence of current tobacco smoking but not in nonsmokers. The two SFTPD single-nucleotide polymorphisms, rs1923536 and rs721917, and haplotypes, including these single-nucleotide polymorphisms or rs2243539, were inversely associated with expiratory lung function in interaction with smoking. In conclusion, SP-D is phenotypically and genetically associated with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive pulmonary disease initiation and development.
authors.affiliation: Cardiovascular and Renal Research, Institute of Molecular Medicine, Univ. of Southern Denmark, Odense, Denmark. glsorensen@health.sdu.dk.
authors.forename: Sofie L
authors.initials: SL
authors.lastname: Johansson
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.forename: René
authors.initials: R
authors.lastname: Holst
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.forename: Niels C G
authors.initials: NC
authors.lastname: Hansen
authors.forename: Allan T
authors.initials: AT
authors.lastname: Hojland
authors.forename: Helle
authors.initials: H
authors.lastname: Wulf-Johansson
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Titlestad
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: Kirsten O
authors.initials: KO
authors.lastname: Kyvik
authors.forename: Grith L
authors.initials: GL
authors.lastname: Sorensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D003430:Cross-Sectional Studies; D003718:Denmark; D005260:Female; D005541:Forced Expiratory Volume; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants
keywords: forced expiratory volume in one second; lung injury; single-nucleotide polymorphisms; surfactant protein D; tobacco smoking