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 years 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 second and forced vital capacity in the presence of current tobacco smoking but not in non-smokers. 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number9
Pages (from-to)L887-L895
Publication statusPublished - 1. May 2014


  • Forced expiratory volume in one second
  • Lung injury
  • Single-nucleotide polymorphism
  • Tobacco smoking
  • surfactant protein D
  • Lung Diseases/chemically induced
  • Prognosis
  • Biomarkers/analysis
  • Humans
  • Middle Aged
  • Pulmonary Surfactants/metabolism
  • Male
  • Smoking/adverse effects
  • Haplotypes/genetics
  • Forced Expiratory Volume
  • Young Adult
  • Polymorphism, Single Nucleotide/genetics
  • Adult
  • Female
  • Cross-Sectional Studies
  • Genetic Association Studies
  • Pulmonary Surfactant-Associated Protein D/genetics
  • Vital Capacity
  • Adolescent
  • Denmark
  • Aged


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