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Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis

Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis
Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis
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.
surfactant protein D, atherosclerosis, single nucleotide polymorphisms, intima-media thickness
0021-9150
7-12
Sorensen, Grith L.
25ac3a15-3fc9-4dab-9fa5-caf89893b845
Bladbjerg, Else Marie
baba633e-a6e8-4e7c-8168-b3bd9e1bc6d5
Steffensen, Rudi
7ddfa342-f036-4fad-945e-ec64094f7c91
Tan, Qihua
1c70380c-2298-495e-80b8-7452e25e7c39
Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Drivsholm, Thomas
135b7e4f-e75d-40d1-9059-da8b174f379b
Holmskov, Uffe
8a55aecd-694c-4d61-849b-9cf32da8ba39
Sorensen, Grith L.
25ac3a15-3fc9-4dab-9fa5-caf89893b845
Bladbjerg, Else Marie
baba633e-a6e8-4e7c-8168-b3bd9e1bc6d5
Steffensen, Rudi
7ddfa342-f036-4fad-945e-ec64094f7c91
Tan, Qihua
1c70380c-2298-495e-80b8-7452e25e7c39
Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Drivsholm, Thomas
135b7e4f-e75d-40d1-9059-da8b174f379b
Holmskov, Uffe
8a55aecd-694c-4d61-849b-9cf32da8ba39

Sorensen, Grith L., Bladbjerg, Else Marie, Steffensen, Rudi, Tan, Qihua, Madsen, Jens, Drivsholm, Thomas and Holmskov, Uffe (2016) Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis. Atherosclerosis, 246, 7-12. (doi:10.1016/j.atherosclerosis.2015.12.037). (PMID:26748346)

Record type: Article

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.

Text
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More information

Accepted/In Press date: 23 December 2015
e-pub ahead of print date: 29 December 2015
Published date: March 2016
Keywords: surfactant protein D, atherosclerosis, single nucleotide polymorphisms, intima-media thickness
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 399246
URI: https://eprints.soton.ac.uk/id/eprint/399246
ISSN: 0021-9150
PURE UUID: 92857e83-b5a5-4569-bf8f-929e5fb7da37
ORCID for Jens Madsen: ORCID iD orcid.org/0000-0003-1664-7645

Catalogue record

Date deposited: 10 Aug 2016 14:12
Last modified: 03 Dec 2019 01:44

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Contributors

Author: Grith L. Sorensen
Author: Else Marie Bladbjerg
Author: Rudi Steffensen
Author: Qihua Tan
Author: Jens Madsen ORCID iD
Author: Thomas Drivsholm
Author: Uffe Holmskov

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