Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death

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dc.contributor.author Yue-Mei, Fan
dc.contributor.author Karhunen, Pekka J
dc.contributor.author Levula, Mari
dc.contributor.author Ilveskoski, Erkki
dc.contributor.author Mikkelsson, Jussi
dc.contributor.author Kajander, Olli A
dc.contributor.author Järvinen, Otso
dc.contributor.author Oksala, Niku
dc.contributor.author Thusberg, Janita
dc.contributor.author Vihinen, Mauno
dc.contributor.author Salenius, Juha-Pekka
dc.contributor.author Kytömäki, Leena
dc.contributor.author Soini, Juhani T
dc.contributor.author Laaksonen, Reijo
dc.contributor.author Lehtimäki, Terho
dc.date.accessioned 2012-06-17T20:13:46Z
dc.date.available 2012-06-17 21:11:53 -
dc.date.available 2012-06-17T20:13:46Z
dc.date.issued 2008 -
dc.identifier.issn 1477-9560 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/65796
dc.description Biomed Central Open access -
dc.description.abstract Background Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD). Methods Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years) Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. Results Whole genome expression profiling showed a significant (p = 0.02) down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V), but not in the aorta or femoral arteries (p = NS for both), as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046). Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71), compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the results were not statistically significant. Conclusion The results suggest that the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle-aged men. -
dc.language.iso en -
dc.title Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-562 -
dc.identifier.doi 10.1186/1477-9560-6-17 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Sisätaudit | en=Internal Medicine| -
dc.journal.title Thrombosis Journal -
dc.journal.volume 6 -
dc.journal.number 17 -
dc.journal.volumepagerange 1-8 -
dc.oldstats 65 -

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