Promoter methylation in coagulation F7 gene influences plasma FVII concentrations and relates to coronary artery disease. Issue 3 (7th February 2012)

• Record Type: Journal Article
• Authors: Friso, Simonetta; Lotto, Valentina; Choi, Sang-Woon; Girelli, Domenico; Pinotti, Mirko; Guarini, Patrizia; Udali, Silvia; Pattini, Patrizia; Pizzolo, Francesca; Martinelli, Nicola; Corrocher, Roberto; Bernardi, Francesco; Olivieri, Oliviero
• Is Part Of: Journal of medical genetics. Volume 49:Issue 3(2012)
• Page Start: 192
• Page End: 199
• Publication Date: 2012-02-07
• Subjects: Epigenetics -- DNA promoter methylation -- coagulation FVII -- F7 polymorphisms -- coronary artery disease -- promoter methylation -- genetics -- nutrition and metabolism -- cardiovascular medicine -- haematology (coagulation) -- haematology (incl blood transfusion) -- ischaemic heart disease -- venous thromboembolism; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2011-100195
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Plasma factor VII concentrations (FVIIa), a marker of coronary artery disease (CAD) risk, are influenced by genetic markers at the promoter site: the A2 allele, due to a 10bp insertion at position −323, is a determinant of lower FVIIa concentrations and reduced CAD risk, while the −402A allele, due to a G>A substitution, confers increased transcriptional activity in vitro resulting in higher FVIIa. Transcriptional regulation of F7 by epigenetic features is, however, still unknown as is the inter-relationship of genetic and epigenetic modifications at the promoter site. Objective: To investigate a possible epigenetic regulation of the F7 gene at the promoter region and its link with functional F7 polymorphisms at the same site. Methods and results: F7 promoter methylation and its relation to F7 promoter polymorphisms in modulating FVIIa and CAD risk were evaluated by methyl-specific PCR and bisulfite sequencing techniques in 253 subjects, of whom 168 had CAD and 88 were CAD-free. Plasma FVIIa was inversely related to methylation in A1A1 and −402GG, that is in the absence of the rare A2 and −402A allele. The higher FVIIa paralleled the lower methylation in A1A1 compared to A2A2 (p=0.035), while no variation in methylation was associated with the different −402G>A genotypes. The modulation of methylation-induced FVIIa concentrations was observed only in A1A1 where the higher methylation resulting in lower FVIIa was prevalent within the CAD-free group compared to the CAD group (p=0.011). Conclusions: Epigenetic regulation through methylation of F7 promoter is associated with CAD by affecting plasma FVIIa concentrations in A1A1 genotypes.