The Role of Factor V Leiden 1691G>A and Prothrombin Gene 20210G>A Mutations in Hypercoagulable State Associated with Venous Thromboembolism among Sudanese Patients

Abstract

Introduction: Venous thromboembolic disease (VTE) is a term encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), or a combination of both. The factor V Leiden (FVL) is the most frequent hereditary cause of VTE in Caucasian but not present in African. The second most frequent genetic cause is prothrombin gene (PRT) mutation. Prevalence in VTE patients varying between 20-50% for FVL and 5-19% for PRT mutation. Presence of FVL mutation increases risk for venous thrombosis 7-fold in heterozygotes and 80-fold in homozygotes. Methods: This was a descriptive, Cross sectional study, in which a total of 176 Sudanese subjects were enrolled in the period between July 2015 and July 2016. Among them, 138 patients (47 males and 91 females),age range 18-90 with clinical features of VTE confirmed by Duplex Doppler US at Khartoum Teaching Hospital were included.Clinical data including age, sex, personal and family history for thromboembolic evidence, known risk factors for VTE were collected. The controls included 38 apparently healthy Sudanese individuals. Controls were free from family history of VTE, Coagulation disorders and risk factors of VTE. Genomic DNA was extracted from EDTA blood and purified using Aidlab Genomic extraction Kit (China) according to the manufacture protocol. FVL (1691G>A) and PRT (20210G>A) mutation were determined by PCR-RFLP method as described by Nahid A et al. with some modifications. Results: The data were collected for 138(65.9% females 34.1% males) with documented VTE, in this study 67% of total VTE patients were over the age of 40. Increased age was noted in the VTE patients with over 34% over the age of 60 years. The controlled subjects included significantly younger individual with 92.1% under the age of 50 and 81.5% under the age of 40 years. The past medical history for the overall sample included: without medical history 29%, POD 23% post natal 16.7%, hypertension 5.8%, pregnancy 5.8%, thyroids disease 4.3%, diabetes mellitus 4.3%, malignancy 2.9%, liver disease 2.2%, CVD 2.2%, sickle cells disease 1.4%, CVA 0.7%, respiratory disease 0.7%, SLE 0.7%. Amplification of a region of FVL using the specified primers gave normal PCR products of 241 bp and normal PCR for 20210G>A gene yields a product sized 345bp is shown in Figure 1. The FVL 1691G>A and PRT 20210G>A mutations was not detected in this study population. Conclusions: Both FVL 1691G>A and PRT 20210G>A mutations were absent and only the normal alleles were detected in VTE patients and controlled groups.