Reduction in coagulation factor VII plasma levels by R353Q but not the −323P0/10 promoter polymorphism in healthy Tunisians

The association between the R353Q and -323P0/10 (10-bp insertion in the promoter region at position -323) factor VII mutations and plasma factor VII levels was investigated in a group of 214 healthy Tunisians. The frequency for the Q allele was 0.253 and that for the 10-bp allele was 0.206, and their distribution was variable, with a high prevalence of the 10-bp allele (0.306) seen in North Tunisia and a high prevalence of the Q allele (0.288) see in the Sahel region. No significant linkage disequilibrium was observed between the two mutations, and the most prevalent haplotype was -323P0/353R (0.589 +/- 0.054). Carriers of the R353Q (P < 0.001), but not -323P0/10 (P = 0.088), factor VII mutations had lower mean factor VII serum concentrations. This reduction in mean serum factor VII was more pronounced among homozygous (Q/Q) carriers and among males (49.9%) compared to females (32.7%). Adjusting for all other variables in the linear regression analysis (sex, age, region, smoking, and R353Q and -323P0/10 mutations), heterozygous carriers of the -323P0/10 and R353Q mutation had on average reductions of 10 units (P = 0.005) and 30 units (P < 0.001) in plasma factor VII, respectively, compared to noncarriers, while homozygote carriers of the R353Q (-43.3, P < 0.001), but not carriers of the -323P0/10 (-6.30, P = 0.356), had significantly lower levels of mean plasma factor VII. These data suggest that part of the previously described effects on FVIIc levels associated with the R/Q polymorphism may be explained by genetic variation in the promoter region of the FVII gene.