title: Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis.
abstract: OBJECTIVE
  Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (pSP-D) and SP-D gene (SFTPD) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis.
  
  
  METHODS
  We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima-media thickness (IMT) and protruding plaques in the right carotid artery. Associations between cardiovascular traits and the levels of pSP-D (n = 687) or two coding SFTPD SNPs rs3088308 and rs721917 (n = 396) were investigated using multiple linear regressions and logistic regressions.
  
  
  RESULTS
  There was no significant association between pSP-D and the presence of plaques or IMT. The SFTPD SNP rs3088308 was nominally associated with the presence of plaques, and rs721917 was nominally associated with IMT. The directions of effects of associations were markedly dependent on current smoking status.
  
  
  CONCLUSIONS
  The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely to be mediated by structural variant SP-D modulation of effects of tobacco smoking and are independent of pSP-D levels. The data warrant confirmation in larger cohorts.
authors.affiliation: Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. Electronic address: glsorensen@health.sdu.dk.
authors.forename: Grith L
authors.initials: GL
authors.lastname: Sorensen
authors.affiliation: Unit for Thrombosis Research, Department of Public Health, University of Southern, Denmark; Department of Clinical Biochemistry, Hospital of Southwest Denmark, Esbjerg, Denmark.
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Bladbjerg
authors.affiliation: Regional Centre for Blood Transfusion and Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.affiliation: Unit for Epidemiology, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Child Health, Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom; National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Jens
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Rigshospitalet, Glostrup, Denmark; The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Drivsholm
authors.affiliation: Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
mesh_terms: D058070:Asymptomatic Diseases; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D016009:Chi-Square Distribution; D003718:Denmark; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D020641:Polymorphism, Single Nucleotide; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D
keywords: Atherosclerosis; Intima-media thickness; Single nucleotide polymorphisms; Surfactant protein D