The Contributions of Thrombophilic Mutations to Genetic Susceptibility to Deep Venous Thrombosis in Iraqi Patients.

Abstract

There is a paucity of data on the contribution of various thrombophilic mutations to the development of venous thrombosis in Iraqi patients. Therefore we designed a study to assess the frequencies of known thrombophilic mutations in this population. 100 consecutive Iraqi patients with color Doppler confirmed deep venous thrombosis of the lower extremities and 100 age- and sex-matched healthy controls were enrolled in the study. Their DNAs were tested by multiplex polymerase chain reaction (PCR) followed by reverse hybridization for factor V Leiden (FVL), the prothrombin (PT) G20210A SNP, and the MTHFR C677T SNP. The factor V A4070G mutation was assessed by restriction fragment length polymorphism-PCR. The prevalence of FVL was 13% in patients versus 2% in controls (odd ratios [OR] 7.3; p=0.007). Patients with recurrent thrombosis also had a significantly higher frequency of Factor V Leiden (OR 8.4, p=0.0007). The prothrombin G20210A, SNP, the factor V A4070G SNP, and the MTHFR 677 TT genotypes were present among patients at 5%, 9%, and 11%, respectively, and among controls at 2%, 6%, and 6%; none of these single mutation prevalence differences were significant. Interestingly, however, when these polymorphisms were studied in aggregate we found that 24% of patients had two or more thrombophilic alleles, compared to only 8% of the controls (OR 3.6; p=0.002). This subgroup included significantly more patients with proximal (p=0.007) and recurrent thrombosis (p=0.012), as well as younger patients (≤40 years) (p=0.026). Two or more thrombophilic alleles, as well as FVL on its own, were both significantly associated with an increased risk of venous thrombosis and recurrence in Iraqi patients. Single thrombophilic mutations on their own were not associated with an increased risk.