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Genetic variants of TNFSF4 and risk for carotid artery disease and stroke
Örebro University, School of Health and Medical Sciences.
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2009 (English)In: Journal of Molecular Medicine, ISSN 0946-2716, E-ISSN 1432-1440, Vol. 87, no 4, p. 337-346Article in journal (Refereed) Published
Abstract [en]

In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730∈±∈30 vs 330∈±∈65 arbitrary units, p∈<∈0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-α; 460∈±∈110 vs 133∈±∈8 arbitrary units, p∈<∈0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.

Place, publisher, year, edition, pages
Springer, 2009. Vol. 87, no 4, p. 337-346
Keywords [en]
Atherosclerosis, Cerebrovascular disease, Gene expression, Inflammation, Single nucleotide polymorphism
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-14213DOI: 10.1007/s00109-008-0412-5ISI: 000264964200002PubMedID: 18998106Scopus ID: 2-s2.0-64149108811OAI: oai:DiVA.org:oru-14213DiVA, id: diva2:391578
Available from: 2011-01-25 Created: 2011-01-25 Last updated: 2017-12-11Bibliographically approved

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Sirsjö, Allan

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