Elsevier

Clinica Chimica Acta

Volume 349, Issues 1–2, November 2004, Pages 199-202
Clinica Chimica Acta

Prevalence in a Tunisian Arabic population of factor VII DNA variants and relation to factor VII plasma levels

https://doi.org/10.1016/j.cccn.2004.06.025Get rights and content

Abstract

Background

A raised plasma factor VII (FVII) level is a risk factor for coronary heart disease. DNA variants have been described to be associated with alteration in FVII levels. The prevalence of FVII polymorphisms is unknown in the Tunisian Arab population.

Methods

In a group of 240 healthy Tunisians, we examined the relationship between levels of FVII coagulant activity (FVIIc) and two polymorphisms in the FVII gene. One polymorphism alters arginine at position 353 to glutamine (R/Q) and the other is a 10 base pair insertion (0/10 bp).

Results

The FVII distribution was in accordance with the Hardy-Weinberg equilibrium. The allele frequencies of Q and 10 bp were 0.212 and 0.235, respectively. There were significant differences in these allelic frequencies between Tunisian and other populations (p<0.001). We observed lower FVIIc levels among subjects with the Q allele compared to RR subjects (RR: 98.17%, RQ/QQ: 57.41%, p<0.0001). For the 0/10 polymorphism, no statistically difference was observed.

Conclusion

The prevalence of the Q allele which was found to be associated with lower plasma FVIIc levels is high in Tunisian population. Further analyses should yield information on the protective role of carrying the Q allele for coronary heart disease.

Introduction

Coagulation factor VII (FVII), a glycoprotein synthesized in the liver, is secreted as a single chain polypeptide of 406 amino acids. It plays a key role in the initiation of blood clotting. After endothelial damage, tissue factor is exposed and binds to FVII, activating it (FVIIa) by proteolytic cleavage at Arg152-Ile153 [1]. Then, FVIIa initiates activation of factors IX and X in the presence of both ionized calcium and phospholipids [2]. This subsequently leads to a blood coagulation via the common pathway. Elevated FVII coagulant activity (FVIIc) levels have been identified as a potential risk factor for cardiovascular disease, especially for fatal coronary events [3]. Plasma levels of FVII are influenced by environmental and genetic factors. It has been reported that a polymorphism at exon 8 of the FVII gene is associated with lower plasma levels of FVII. This polymorphism arises from a base substitution of guanine to adenine in codon 353, leading to a substitution of arginine by glutamine in the protein product [4]. For this polymorphism, alleles were designated as R and Q, respectively. Another 10 base pair insertion, designated as 0/10 bp polymorphism which is located in the promoter region of the factor VII gene, was also found to have a genotype effect on plasma FVIIc levels [5].

It has been reported that differences in FVII activity levels and in genotype frequencies depend on the ethnic groups [6]. In addition, to our knowledge, the prevalence of factor VII gene polymorphisms has not yet been studied previously in any Arabic country. The aim of this study was to determine genotype and allelic frequencies of FVII gene polymorphisms and to investigate the relationship between FVII levels and gene polymorphisms in Tunisian Arab population. This healthy population study will constitute a reference for subsequent studies of patients with heart disease.

Section snippets

Subjects

A total of 240 healthy volunteers (152 males and 88 females, aged 20–60 years), recruited from blood donors, were investigated. All of them were unrelated and living in Tunisia. All participants declared themselves free of cardiovascular disease and diabetes. None of the women was taking oral contraceptives or other drugs that might affect factor VII levels. Blood samples were collected in plastic tubes containing 1/10 volume of 0.129 ml/l buffered sodium citrate. FVIIc was determined using a

Results

A total of 240 individuals were analyzed for the two polymorphisms R353Q substitution and 0/10 bp insertion. Three genotype (R/R, R/Q, Q/Q and 0/0, 0/10 10/10) were found in each polymorphism in this study. The genotypes frequencies are given in Table 1. The genotype distribution was in accordance with the Hardy-Weinberg equilibrium using the Chi-square test (p>0.05). The allelic frequencies were as follows: for R/Q alleles 0.788 and 0.212, respectively, and for 0/10 bp alleles 0.765 and 0.235,

Discussion

Geographical differences in FVII genotypes and phenotypes have been reported and the complete absence of information on Tunisian population led us to design this study. Our results showed that allelic frequencies of FVII gene polymorphisms in Tunisian Arab population are significantly different from those reported in other populations. The estimated frequencies of Q and 10 bp alleles in Tunisians are significantly higher than those of the Northern and Southern Europeans [6]. They were also

References (15)

There are more references available in the full text version of this article.
View full text