Grith L Sorensen1, Else Marie Bladbjerg2, Rudi Steffensen3, Qihua Tan4, Jens Madsen5, Thomas Drivsholm6, Uffe Holmskov7. 1. Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. Electronic address: glsorensen@health.sdu.dk. 2. Unit for Thrombosis Research, Department of Public Health, University of Southern, Denmark; Department of Clinical Biochemistry, Hospital of Southwest Denmark, Esbjerg, Denmark. 3. Regional Centre for Blood Transfusion and Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. 4. Unit for Epidemiology, Department of Public Health, University of Southern Denmark, Odense, Denmark. 5. 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. 6. 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. 7. Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
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.
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.