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) seen 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 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 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. Am.

Identification of genetic defects underlying FVII deficiency in 10 patients belonging to eight unrelated families of the North provinces from Tunisia

“…A few Tunisian studies were interested in the distribution of some polymorphisms (M1/M2 and P0/P10) in patients with FVII deficiency and healthy groups from different Tunisian regions demonstrate that the most frequent alleles are M1/M1 and P0/P0 in all the studied groups and also in groups from the North of Tunisia [4,5]. This distribution is confirmed in our patients who are from the North and in whom we identified only one allele M1/M2 in one patient/7 unrelated patients and we found the allele P0/P10 only in 2 patients.…”

A novel missense mutation close to the charge-stabilizing system in a patient with congenital factor VII deficiency

“…1, two heterozygous mutations in the F7 gene of the patient were identified by direct genomic DNA sequencing, including a G-to-A transition at nucleotide 15975 in the splice receptor site of intron 6 (IVS6-1G>A) and a C-to-T transition at nucleotide 16750 in exon 8 with the substitution of Ser (TCC) for Phe (TTC) at amino acid 190 (p.Ser190Phe). The rare polymorphisms of F7 lowering plasma levels were not detected [10][11][12]. The patient's mother was heterozygous for F7 15975 G>A (IVS6-1G>A), whereas his father was heterozygous for in F7 were found in his sister and no other variants were found in this family.…”

Association analysis of genetic polymorphisms of factor V, factor VII and fibrinogen β chain genes with human abdominal aortic aneurysm

“…Most of the data have shown that the insertion of a decanucleotide fragment at position −323 in the promoter region of FVII is related to lower coagulation activity and antigen level of factor VII (10,41,42). On the other hand, Mtiraoui et al (43) did not find such correlation in a population of healthy Tunisians. The elevated activity of factor VII may indicate a tendency for thrombosis, thus suggesting that a decreased level of circulating factor VII may exert a protective effect on their development.…”