An Arab selective gradient in the distribution of factor V G1691A (Leiden), prothrombin G20210A, and methylenete...

Abstract

Venous thrombosis (VTE) is a multi-factorial disease resulting from the interaction of genetic and environmental risk factors. Among the inherited factors are factor V (FV) G1691A (FV Leiden)[1], prothrombin (PRT) G20210A [2], and methylenetetrahydrofolate reductase (MTHFR) C677T [3] single nucleotide polymorphisms (SNPs). In FV Leiden, an arginine is substituted by glutamine at amino acid residue 506, which renders FVa resistant to degradation by activated protein C [1]. The PRT G20210A SNP, a G to A transition in the 3′ untranslated region of the PRT gene, is associated with increased PRT levels [2]. While both FV Leiden and G20210A SNPs are present at varying rates in Caucasians [4], and are virtually absent from Africans and Asians [5], the MTHFR C677T is found in many populations with a marked heterogeneity in its distribution, exemplified by its low incidence in Africa and Indian subcontinent [6], and higher rates in North America, Europe [7], and Japan. Insofar as the incidence of FV Leiden, PRT G20210A, and MTHFR C677T SNPs among Arabs is poorly defined, we assessed the incidence of these three SNPs in four distinct Arab communities: Lebanon, Tunisia, Bahrain, and Saudi Arabia. Study subjects comprised 698 Lebanese (288 males and 410 females), 313 Tunisian (129 males and 184 females), 193 Bahraini (150 males and 43 females), and 149 Saudi (69 males and 80 females) healthy subjects. Genotyping was carried out by PCR-RFLP analysis using MnlI, HindIII, and HinfI digestion for detecting FV Leiden, PRT G20210A and MTHFR C677T, respectively. Allele frequencies were determined using the gene …