Thrombosis risk in carriers of the factor V Leiden mutation: is it associated with a defined skin color?

Factor V Leiden (FVL; G1691A) is an autosomal dominant mutation with a high risk for thrombosis. Speculation that founders of FVL lived in the Middle East is supported by a prevalence of FVL that is higher in Arabs residing in Israel, Jordan, Lebanon, and Syria (12-14%) than in other white populations like Europeans (4-5%, up to 15% in the South of Sweden). We sought to verify the appropriate use of skin color as a clinical sign by which Arab individuals in Kuwait are included or excluded from testing for FVL. After institutional approval, 200 healthy Arabs residing in Kuwait consented to participate. Skin type was distinguished for the participants by Fitzpatrick natural skin color classification: 76 (38%) skin type II (white), 96 (48%) Mediterranean skin type IV (brown), and 28 (14%) skin type VI (black). FVL was tested by real-time PCR, and the percentage of carriers was calculated in each group. FVL was positive in 17 (8.5%) of the total subjects: 8 (10.5%) skin type II, 7 (7.3%) skin type IV, and 2 (7.1%) skin type VI. Therefore, FVL shows an even distribution in Arabs, and all Arabs residing in Kuwait should be tested for FVL irrespective of skin color.

High prevalence of activated protein C resistance and factor V Leiden mutation in an Arab population and patients with venous thrombosis in Kuwait.

INTRODUCTION: Activated protein C resistance (APC-R) because of clotting factor V Leiden mutation (FVL; Arg506Gln; G1691A) is a risk factor for the development of venous thromboembolic disorders (VTE). APC-R/FVL was reported to be very high in White patients with VTE (15% to 65%) and healthy populations (1% to 15%), and to be very low or absent in non-White patients. Studies on Arab patients and populations were very inconsistent. This study reports APC-R and FVL in Arabs living in Kuwait. MATERIALS AND METHODS: Whole venous blood samples were collected from 400 patients with VTE and 200 healthy controls, all of whom were of Arab ethnicity living in Kuwait. The samples were used to separate plasma for an APC-R test, and DNA extraction for polymerase chain reaction and restricted fragment length polymorphism were performed. APC-R was on an automated hemostasis analyzer, and values less than 2.0 were reported as APC-R. Polymerase chain reaction and restricted fragment length polymorphism tests were performed using standard methods, and the results were reported as normal wild-type homozygous GG, FVL homozygous AA, or FVL heterozygous GA. RESULTS: Sixty-three out of 400 patients (15.75%) and 4 out of 200 healthy controls (2%) had APC-R and at least one copy of FVL. Fifty-one patients and 4 controls were heterozygous whereas only 12 patients were homozygous. CONCLUSION: The prevalence of APC-R and FVL is quite high in Arabs living in Kuwait, being comparable with the prevalence reported in Whites, although being toward the lowest values reported there.

Factor V Leiden mutation in Arabs in Kuwait by real-time PCR: different values for different Arabs.

Factor V Leiden (FVL) mutation (G1691A) is a risk factor for development of venous thromboembolic disorders. FVL was found mostly in Caucasians (1-15%) but was almost absent in non-Caucasians. Studies on Arab patients and populations revealed very inconsistent results. This study reports FVL in Arabs living in Kuwait with a focus on the nationality of the Arab subjects studied. Whole-blood samples were collected from 400 healthy Arabs who were 268 Kuwaitis (67%), 50 Syrians (12.5%), 34 Jordanians (8.5%), 8 Palestinians (2%) and 40 Egyptians (10%). DNA extraction was carried out for these blood samples and real-time PCR was performed to detect the presence of FVL. Generally, 36 cases (9%) had the mutation (33 were heterozygous and 3 were homozygous), with an allelic frequency of 0.049. The prevalence of FVL differed in different Arabic cases: Kuwaitis 4.5%, Egyptians 15%, Syrians 16%, Jordanians 23.5% and Palestinians 25%. The allelic frequency was 0.022 in the Kuwaitis and 0.088-0.132 in non-Kuwaitis. The three homozygous cases were from Syria, Jordan and Egypt. In conclusion, the prevalence of FVL in Arabs living in Kuwait is as high as in Caucasians. There is a difference in prevalence among Arabs themselves, being relatively lower in Kuwaitis than in non-Kuwaitis.

Whole-blood polymerase chain reaction and restriction fragment length polymorphism: a simplified method by microwave irradiation.

OBJECTIVES: The aim of the present study was to develop a simple, quick and cheap method to process whole-blood samples for the molecular techniques polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) without the use of expensive reagents or sophisticated machines. MATERIALS AND METHODS: Venous whole-blood samples were collected from 40 individuals. The samples were frozen at -80 degrees C, and then rapidly thawed at 37 degrees C. Each sample was incubated with distilled water, then boiled in a microwave and centrifuged. The supernatant was taken directly for PCR and RFLP. For comparison, PCR and RFLP were performed on DNA purified from the same samples using the phenol-chloroform method and two commercial DNA extraction kits. RESULTS: PCR/RFLP results using the presented method were qualitatively similar to those obtained by DNA extracted using the other three methods. CONCLUSION: The presented method proved to be a simpler and cheaper way of processing whole-blood samples for PCR and RFLP analyses.

Factor V Kuwait: a novel mutation in the coagulation factor V gene discovered in Kuwait.

OBJECTIVE: It was the aim of this study to report a new point mutation in the clotting factor V gene in the general Arab population. SUBJECTS AND METHODS: The HR2 haplotype was tested in 288 Arabs living in Kuwait--188 patients with venous thromboembolic disorders (VTE) and 100 healthy subjects--using polymerase chain reaction and restriction fragment length polymorphism techniques. The presence of the new mutation was verified by DNA sequencing. RESULTS: Two (1.06%) VTE patients had guanine instead of the wild-type adenine at nucleotide number 3935 (A3935G) of the factor V gene. This mutation caused a histidine to arginine change in amino acid number 1254 of the factor V molecule. The new mutation is termed 'factor V Kuwait' (His1254Arg) and was absent in the 100 healthy subjects. CONCLUSION: It appears that factor V Kuwait could be a risk factor for developing VTE in Arabs. A larger study is needed to confirm this observation.