Coagulation Factor II

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OMIM Number

176930

NCBI Gene ID

2147

Uniprot ID

P00734

Length

20327 bases

No. of Exons

14

No. of isoforms

1

Protein Name

Prothrombin

Molecular Mass

70037Da

Amino Acid Count

622

Genomic Location

chr11:46719180-46739506

Gene Map Locus
11p11.2

Description

Normal blood coagulation is a complex process, involving activation of different plasma proteins, ultimately resulting in the formation of fibrin. Factor II, or prothrombin, is one of the components of this complex cascade. When activated, prothrombin gets converted to thrombin, which is a serine protease responsible for the cleavage and activation of fibrinogen to fibrin resulting in clot formation. A deficiency of prothrombin leads to a defect in the clotting cascade, resulting in hypoprothrombinemia, characterized by unrestricted bleeding. On the other hand, certain mutations in the prothrombin gene, cause overproduction of the FII protein, resulting in deep vein thrombosis, or venous thromboembolism.

Molecular Genetics

The F2 gene is about 20Kb long, and the prothrombin protein weighs 70kDa. Activation of prothrombin takes place on the surface of a phospholipid membrane, where both the amino end of prothrombin and factors Va and Xa are bound in Ca-dependent interactions. Factor Xa removes the activation peptide and cleaves the remaining part into light and heavy chains. The most well-known prothrombin allele variant is the G20210A mutation. This mutation occurs in the 3' untranslated part of the gene, and is expected to confer some form of added stability to the protein, ensuring excess plasma levels. Along with the Factor V Leiden mutation, the G20210A mutation is one of the leading causes of venous thromboembolism.

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinical SignificanceCondition(s)HGVS ExpressionsdbSNPClinvar
NM_000506.4:c.*97G>ALebanonNC_000011.10:g.46739505G>APathogenic,Risk factor,Uncertain SignificanceThrombophilia due to thrombin defect; Stroke, Ischemic; Coronary Heart Disease, Susceptibility to, 1; Budd-Chiari Syndrome; Pregnancy Loss, Recurrent, Susceptibility to, 1; Thrombophilia due to Activated Protein C ResistanceNG_008953.1:g.25313G>A; NM_000506.4:c.*97G>A179996313310

Other Reports

Bahrain

Almawi et al. (2005b) studied the prevalence of the prothrombin G20210A SNP amongst Arab populations. A total of 194 healthy Bahraini subjects were compared to Lebanese, Tunisian, and Saudi Arabian subjects. PCR-RFLP using HindIII was used to genotype the PRT gene. The G20210A SNP was detected at a prevalence rate of 0.0052 in the Bahraini population. This low prevalence was comparable to its non-detection in the Saudi Arabian subjects, but was significantly lower than in the Lebanese and Tunisian patients. Of the subjects, 1.0% were positive for G20210, and all had the G/A genotype. The overall average genetic differentiation between the populations was 0.005 for PRT G20210A. [Almawi WY, Keleshian SH, Borgi L, Fawaz NA, Abboud N, Mtiraoui N, Mahjoub T. Varied prevalence of factor V G1691A (Leiden) and prothrombin G20210A single nucleotide polymorphisms among Arabs. J Thromb Thrombolysis. 2005b; 20(3):163-8]

[See also: Lebanon, Saudi Arabia, Tunisia > Almawi et al., 2005b].

Iraq

In 1977, Al-Mondhiry studied the occurrence and pattern of inherited bleeding syndromes in Iraq. During the first fourteen months of a prospective on-going study at a major university center, 116 patients from 62 families were diagnosed as having inherited bleeding syndromes. All patients were referred because of moderate to severe bleeding diatheses. They included 62 hemophiliacs 32 patients with von Willebrand's disease (VWD), 9 with Christmas disease (CD), 6 with afibrinogenemia, 1 with prothrombin deficiency, and 6 were thought to have platelet dysfunction.

Kuwait

Elshafaay et al. (2008) studied 1000 couples with a history of Recurrent Pregnancy Loss (RPL). Cytogenetic studies identified only 44 patients with chromosomal abnormalities. Of the remaining patients, a sub-group of 100 female patients were tested for the presence of Factor II G20210A mutation. The results found no statistically significant difference between the proportion of patients with this mutation and the control cases (100 females without any history of RPL).

Lebanon

Almawi et al. (2005a) undertook a case control study to understand the prevalence of the prothrombotic mutations G1691A FV-Leiden, factor II G20210A, and MTHFR C677T mutations. One hundred and ninety eight Lebanese patients (84 males, 114 females), diagnosed with venous thromboembolism (VTE) were compared to 697 healthy age and gender matched controls. Diagnosis of VTE was performed using Doppler ultrasound, duplex scan, D-dimer levels, and phlebogram. Mutation analysis of the subjects was performed by PCR followed by RFLP using HindIII for factor II. Multiple triple regression model analysis was also performed. The patients showed a significantly higher frequency of the factor II G20210A mutation (.0581) compared to the control (.0294). The factor II G/A and A/A genotypes were higher in the patient group (18.7% and 0.5%) compared to the control group (3.6% and 0%). Logistic regression analysis showed that individuals below 45 years of age were 5.5 times more prone to developing VTE. The highest risk for development of the disease was seen to be exerted by the combined presence of FV-Leiden and factor II G20210A mutations. In a second study conducted to compare the prevalence of the prothrombin G20210A SNP amongst Arab populations, Almawi et al. (2005b) found that the prevalence of the PRT G20210A SNP was significantly higher amongst the 698 healthy Lebanese subjects (0.0136), when compared to a Bahraini and Saudi population. Of the subjects, 3.6% were positive for G20210, and all had the G/A genotype. The overall average genetic differentiation between the populations was 0.005 for PRT G20210A.

[See also: Bahrain > Almawi et al., 2005b].

Saudi Arabia

Fawaz et al. (2004) carried out a molecular study to assess the prevalence of the prothrombin (PRT) G20210A mutation in sickle cell disease (SCD) patients and healthy controls. Study subjects comprised 87 SCD patients (38 males and 49 females; mean age 23.10 ± 14.15 years) and 105 controls (65 males and 40 females; mean age 32.28 ± 15.00 years). All patients were Saudi nationals from Eastern Saudi Arabia. PCR-RFLP analysis was used to detect the PRT G20210A mutation. The prevalence of PRT G20210A did not differ between patients and controls, because two patients were heterozygous (G/A; 2.30), whereas none of the controls was a carrier (P = 0.397). This low frequency (0.0%) of PRT G20210A was seen among healthy individuals in Eastern Saudi Arabia (Dammam) in this study, in agreement with a study on its prevalence in Western Saudi Arabia (Jeddah), where PRT G20210A occurs at a rate of 1.1%. The prevalence of PRT G20210A (P = 0.397) was not different between patients and controls, thereby giving no support to an association of PRT G20210A with SCD. This result led Fawaz et al. (2004) to conclude that the PRT G20210A, as inherited hypercoagulability risk factor, has a low impact in the pathogenesis of SCD and/or its complications.

Almawi et al. (2005b) studied the prevalence of the prothrombin G20210A SNP amongst Arab populations. A total of 149 healthy Bahraini subjects were compared to Lebanese, Tunisian, and Saudi Arabian subjects. PCR-RFLP using HindIII was used to genotype the PRT gene. The G20210A SNP was not detected among the Saudi population. [Almawi WY, Keleshian SH, Borgi L, Fawaz NA, Abboud N, Mtiraoui N, Mahjoub T. Varied prevalence of factor V G1691A (Leiden) and prothrombin G20210A single nucleotide polymorphisms among Arabs. J Thromb Thrombolysis. 2005b; 20(3):163-8]

[See also: Bahrain > Almawi et al., 2005b].

Mammo et al. (2007) reported the incidences of five prothrombotic gene polymorphisms among Saudi Arabians. The data for this study came from the Saudi Thrombosis and Familial Thrombophilia Registry. The subjects were healthy consenting donors from different regions, tribes, and origins in Saudi Arabia. Between 2001 and 2005, DNA samples from 902 Saudis (793 men and 109 women) were collected and genotyped. The Prothrombin G20210G>A mutation was tested in 884 of these subjects. Heterozygous carrier rate for this mutation was found to be 1%, while none of the subjects were homozygous rare allele carriers.

Tunisia

In a study conducted to compare the prevalence of the prothrombin G20210A SNP amongst Arab populations, Almawi et al. (2005b) found that the prevalence of the PRT G20210A SNP was significantly higher amongst the 313 healthy Tunisian subjects (0.0136), when compared to a Bahraini and Saudi population. Of the subjects, 2.6% were positive for G20210, and all had the G/A genotype. The overall average genetic differentiation between the populations was 0.005 for PRT G20210A. [Almawi WY, Keleshian SH, Borgi L, Fawaz NA, Abboud N, Mtiraoui N, Mahjoub T. Varied prevalence of factor V G1691A (Leiden) and prothrombin G20210A single nucleotide polymorphisms among Arabs. J Thromb Thrombolysis. 2005b; 20(3):163-8]

[See also: Bahrain > Almawi et al., 2005b].

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