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

Al-Jawahara Center for Molecular Medicine, Genetics and Inherited Diseases, Arabian Gulf University, Manama, BahrainThe association between the R353Q and -323P0/10 (10-bp insertion in the promoter regionat position -323) factor VIImutations and plasma factor VIIlevels was investigated in agroup of 214 healthy Tunisians. The frequency for the Q allele was 0.253 and that for the10-bp allele was 0.206, and their distribution was variable, with a high prevalence of the10-bpallele(0.306)seeninNorthTunisiaandahighprevalenceoftheQallele(0.288)seeninthe Sahel region. No significant linkage disequilibrium was observed between the twomutations, and the most prevalent haplotype was -323P0/353R (0.589 ± 0.054). Carriers ofthe R353Q (P <0.001),butnot-323P0/10 (P = 0.088), factor VIImutations had lower meanfactor VII serum concentrations. This reduction in mean serum factor VIIwas more pro-nouncedamonghomozygous(Q/Q)carriersandamongmales(49.9%)comparedtofemales(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 -323P0/10and R353Q mutations 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 homozygotecarriers 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 ofthepreviouslydescribedeffectsonFVIIclevelsassociatedwiththeR/Qpolymorphismmaybe explained by genetic variation in the promoter region of the FVII gene. Am. J. Hematol.79:11¯–16, 2005.