Association Between Factor VII Polymorphisms and Blood Pressure

Abstract

Abstract-The purpose this study was to determine whether Arg353Gln and Ϫ323Del/Ins polymorphisms of factor VII (FVII) are related to blood pressure levels and hypertension. Subjects were drawn from the Stanislas Cohort, a longitudinal, familial French cohort examined twice since 1994. The "blood pressure study" included 1342 subjects free of medication use that could affect blood pressure. The "hypertension study" included 645 normotensive and 77 hypertensive adult subjects. Association with hypertension was also studied in 547 hypertensives enrolled in a clinical trial and in 624 normotensives drawn from the Stanislas Cohort. In the "blood pressure study," parents with the 353Gln or Ϫ323Ins allele had lower blood pressures than did noncarriers at each examination, independent of covariates (0 [1][2][3][4] and blood pressure (BP) and/or hypertension have been described. Association studies cannot establish whether abnormalities of rheology and coagulation occur as a consequence of the higher BP or whether these could be factors that contribute to high BP. However, data suggest that hemorheologic factors may be implicated in BP homeostasis. Thrombin, in addition to converting fibrinogen to fibrin, can interact with cell-surface receptors and induce several intracellular pathways. 5,6 Proangiogenic activities of thrombin have been described, 5 and thrombin can also modulate vascular tone 7 and have proinflammatory properties. 8 All of these factors can play a role in initiating and maintaining an elevation in BP.Factor VII (FVII) is a key factor in the coagulation cascade leading to the production of thrombin. FVII also elicits several cellular responses, such as angiogenesis 9 -11 and inflammation, 12,13 that may be related to hypertension, and associations between FVII and BP have been found. 14 -16 Genetic variations in the FVII gene, the Arg353Gln and the Ϫ323Del/Ins polymorphisms, have been related to FVII levels and coagulant activity. [17][18][19][20] An association between BP and the Arg353Gln polymorphism was described in a genetic isolate. 21 Therefore, the purpose of this study was to investigate the association of these 2 polymorphisms with BP levels and hypertension in a large, family-based population. Methods BP StudyThe study population was selected from the Stanislas Cohort 22 For the present study, 1342 individuals (657 men and 686 women from 424 families) were selected on the basis of the following criteria: (1) subjects were present at both the first (T0) and second (Tϩ5) examinations; (2) data from both examinations and information on FVII Arg353Gln and Ϫ323Del/Ins genotypes were available; and (3) at each visit, there was no indication of antihypertensive, lipidlowering, or anti-inflammatory drug use. Hypertension Studies Sample Group 1The normotensive subjects were drawn from the "blood pressure levels study" sample population. There were 295 fathers and 350 mothers with a systolic blood pressure (SBP)/diastolic blood pres-

Association between polymorphisms in the coagulation factor VII gene and coronary heart disease risk in different ethnicities: a meta-analysis

“…Vascular tone, inflammation, blood viscosity, and angiogenesis can play roles in initiating and maintaining an elevation in BP and, therefore, are potential mechanisms contributing to the association between FACTOR VII and risk factors like smoking, diabetes, hypertension, and mental stress. The FVII polymorphisms were reported to be associated with decreased blood pressure and a decreased risk of hypertension [36], suggesting that these FVII variants might influence cardiovascular risk through mechanisms other than thrombosis.…”

Functional Epistatic Interaction between rs6046G>A in F7 and rs5355C>T in SELE Modifies Systolic Blood Pressure Levels

“…rs6046G>A in F7 was shown to be associated with increased F7 plasmatic levels [15]. More interestingly, this SNP was reported to have a role in protection against myocardial infarction in two different studies performed on Italian populations [29], [30].…”

“…These genetic variants were candidate markers for cardiovascular disease (CVD) risk factors, specifically involved in the predisposition to essential HTN (rs1799752Ins>del in ACE ), in the development of atherosclerotic plaques and in the progression of atherosclerosis ( rs5882A>G in CETP , rs1801133C>T in MTHFR rs662A>G in PON1 and rs1800629G>A in TNF ) [12]. In addition, rs5355C>T in SELE [13], [21], rs1800790G>A in FGB [14], rs6046G>A in F7 [15], rs328C>G in LPL [16], [22] were chose based on our previous published studies that found these SNPs associated with BP levels and/or HTN in European populations [12]–[16], [21], [22]. Finally, rs3025058T>Ins in MMP3 was selected from an internal investigation showing a link between this genetic variant and BP levels.…”

Epistatic study reveals two genetic interactions in blood pressure regulation

“…Inflammation, blood coagulation cascade, cellular adhesion molecules and lipid metabolism all appear to have significant roles [6-8]. While aspects of BP regulation may be the product of an inflammation stimulus [6,9], thrombin is also known to induce several intracellular pathways [7], to modulate vascular tone [7,10] and to have pro-inflammatory effects [7]. Growing evidence also suggests that cellular adhesion molecules and apolipoproteins are closely related to HT [8,11].…”

“…Growing evidence also suggests that cellular adhesion molecules and apolipoproteins are closely related to HT [8,11]. All of these factors may be involved in initiating and maintaining elevated BP levels [7]. Overall, however, the genetic factors associated with BP are poorly characterized and the effects of metabolic pathways highlighted by previous studies remain unclear.…”