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a Address correspondence to this author at: Department of Laboratory Medicine, St. Georges Hospital, P.O. Box 166378-6417, Beirut, Lebanon. Fax 961-1-582560.
Departments of
1
Laboratory Medicine,,
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Cardiology,, and,
3
Obstetrics and Gynecology, St. Georges Hospital, Beirut, Lebanon
4
Faculty of Health Sciences, Balamand University, Beirut, Lebanon
To the Editor:
Factor V (FV), a 330-kDa procofactor, is a plasma protein that acts in concert with other plasma factors in regulating the blood coagulation cascade (1). Upon its proteolysis by factor Xa and/or thrombin, factor Va is inactivated by proteolysis by activated protein C (1)(2). A defect in FV hydrolysis brought about in part by resistance to activated protein C hydrolysis translates into poor anticoagulant activity, leading to thrombosis and other disorders of poor anticoagulation (3)(4)(5). Factor V mutation-Leiden (FV-Leiden) is a specific point mutation, identified as a G-A substitution in nucleotide 1691 in the factor V gene that leads to Arg506-Gln conversion (2) and is associated with hypercoagulability and increased risk of venous thromboembolism. The prevalence of FV-Leiden is high among venous thromboembolism patients (20–60%) compared with otherwise healthy individuals (2–13%) (6)(7). FV-Leiden has been described as a predisposing as well as an additional risk factor for venous thrombosis (3), pulmonary embolism (5), and to a lesser extent coronary artery disease (8). However, the latter remains to be established in light of reports disputing any link between FV-Leiden and coronary artery disease (3)(9).
High prevalence of FV-Leiden has been reported in Caucasians (Europeans and Arabs) but not in non-Caucasians (Africans, Asians, and Eskimos) (10)(11)(12), thus suggesting a single origin of the mutation (13). In view of its role as the most common inherited predisposing factor for venous thrombosis and other disorders of poor anticoagulation (14), coupled with its preferential distribution in selective areas and in different ethnic groups (6)(12), we assessed the prevalence of the FV-Leiden mutation in Lebanon. Our results were compared to those of other countries, in particular Eastern Mediterranean countries. The data obtained support earlier findings regarding the high prevalence of FV-Leiden among Caucasians (12)(15) and suggest that this mutation arose in the Eastern Mediterranean.
Healthy, unrelated Lebanese individuals (n = 155) of both sexes and of different age groups from the five provinces of Lebanon, representing the two major religious groups, were recruited into the study after signing a consent form. All institutional ethics requirements were met. Total genomic DNA was extracted from peripheral blood mononuclear cells by incubation of the cells in a proteinase K-containing lysis buffer, followed by extraction with phenol-chloroform, and precipitation with 7.5 mol/L ammonium acetate and ice-cold absolute ethanol. FV-Leiden was assessed by PCR, followed by hybridization of PCR products with wild-type (G) and mutant (A) DNA probes and detection by DNA enzyme immunoassay according to the manufacturer’s instruction (SORIN). The results were interpreted as follows: FV-Leiden non-carriers, positive G-negative A; FV-Leiden heterozygote, positive G-positive A; and FV-Leiden homozygote, negative G-positive A.
The prevalence of FV-Leiden was determined for 155 healthy, unrelated
Lebanese subjects (mean age, 32 ± 11 years). The subjects,
recruited from different provinces, were of both sexes (81 males and 74
females) and represented the two major religious groups (60 Moslems and
95 Christians). All participants were free of blood coagulation
disorders, and none was on anticoagulant therapy. FV-Leiden was present
in 22 of 155 participants (14.2%; Table 1
).The mean age of FV-Leiden carriers was similar to that of
FV-Leiden-negative individuals (32.2 ± 11.4 years and 32.3
± 11.3 years, respectively; P = 0.96). The frequencies
of FV-Leiden were similar in females and males (13 of 74 vs 9 of 81,
respectively; P = 0.25) and in Christians and Moslems
(16 of 95 vs 6 of 60, respectively; P = 0.39).
Heterogeneity in FV-Leiden distribution was noted among the different
provinces of Lebanon, exemplified by the high prevalence in Mount
Lebanon and the low prevalence in South Lebanon (7 of 43 and 1 of 32,
respectively; P = 0.21; Table 1
), thus suggesting
differential demographic distribution of FV-Leiden. We found 21
heterozygotes and 1 homozygote. The homozygote, a 61-year-old male, had
no signs of thrombosis at the time of specimen collection. The observed
homozygote-to-heterozygote ratio was consistent with Hardy-Weinberg
equilibrium (p = 0.858; 2pq = 0.135, and q = 0.00645).
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The high prevalence of FV-Leiden in Lebanon (14.2%) was similar to prevalences in Syria (13.6%; A. Nehme, personal communication), Greece-Cyprus (13.4%) (6), Jordan (12.3%) (16), and Turkey (7.4%) (17), further supporting the concept (13) that the FV-Leiden mutation arose in the Eastern Mediterranean basin. FV-Leiden is common in countries with predominantly Caucasian populations [e.g., Sweden (11.1%) (18) and Germany (7.13%) (19)] and also in countries associated with significant migrations of Lebanese/Syrians and Greeks [e.g., UK (8.9%) (6), Argentina (5.12%) (11), Australia (20), and Spain (3.33%) (4)]. In contrast, FV-Leiden is nearly absent in Senegalese (6), African-Americans (15), Koreans (21), Japanese (22), and among Greenland Inuits (23), further confirming the preferential prevalence of FV-Leiden among Caucasians, as suggested (10)(12)(15).
FV-Leiden is the largest inherited risk factor of venous thrombosis (14). However, the pathogenesis of venous thrombosis is multifactorial, including inherited and non-inherited risk factors (24). Whereas our results do not support random and indiscriminate screening for FV-Leiden, they do recommend screening for FV-Leiden in relatives of FV-Leiden carriers.
References
The following articles in journals at HighWire Press have cited this article:
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  R. Jabbour, A. Taher, A. Shamseddine, and S. F. Atweh Moyamoya Syndrome With Intraventricular Hemorrhage in an Adult With Factor V Leiden Mutation Arch Neurol, July 1, 2005; 62(7): 1144 - 1146. [Abstract] [Full Text] [PDF]
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 N. A. Al-Allawi, J. M.S. Jubrael, and F. A. Hilmi Factor V Leiden in Blood Donors in Baghdad (Iraq) Clin. Chem., March 1, 2004; 50(3): 677 - 678. [Full Text] [PDF]
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