title: Reduction in coagulation factor VII plasma levels by R353Q but not the -323P0/10 promoter polymorphism in healthy Tunisians.
abstract: 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.
authors.affiliation: Hematological and Autoimmune Diseases Research Unit, Faculté de Pharmacie de Monastir, Université du Centre, Tunisia.
authors.forename: Nabil
authors.initials: N
authors.lastname: Mtiraoui
authors.forename: Nesrine
authors.initials: N
authors.lastname: Aboud
authors.forename: Hatem
authors.initials: H
authors.lastname: Bouraoui
authors.forename: Sondes
authors.initials: S
authors.lastname: Haizem
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Gris
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Hala
authors.initials: H
authors.lastname: Tamim
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D005167:Factor VII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005843:Geography; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012016:Reference Values; D014416:Tunisia
chemical_list: D005167:Factor VII