GENETIC MODULATION OF COAGULATION-FACTOR-VII PLASMA-LEVELS - CONTRIBUTION OF DIFFERENT POLYMORPHISMS AND GENDER-RELATED EFFECTS

We studied the relationships among different polymorphisms of FVII gen e in determining FVII levels, in a sample of 335 male and female Itali an volunteers. The hypervariable region 4 (HVR4), the promoter decanuc leotide insertion (-323 0/10 bp) and the R353Q polymorphisms of FVII g ene were evaluated. The association of HVR4 or -323 0/10 bp polymorphi sm with plasma FVII levels differed between gender (lnteraction term: p = 0.02 and p = 0.03, respectively), showing stronger effect in males than in females. In males, the R353Q and the HVR4 polymorphisms showe d an incremental influence on FVII variance (F = 8.9, p < 0.001 and F = 4.4, p = 0.01, respectively). Moreover, the effects of Q and 10 bp a lleles on the reduction of FVII activity levels were significantly pot entiated by the presence of H7 allele of HVR4 (Interaction term p = 0. 03 for R353QHVR4 and p = 0.03 for -323 0/10 bp*HVR4). In conclusion, the effect of FVII polymorphisms on FVII levels was gender dependent a nd derived from a complex interaction among them. The HVR4 polymorphis m seems to add an independent, albeit small, contribution to the regul ation of FVII plasma levels.