Characterization of Factor-V Leiden G1961A and prothrombin G20210A polymorphisms as biomarkers in Sickle cell disease in Uganda

Abstract

Sickle cell anemia (SCA) is a common inherited qualitative haemoglobinopathy. It is common in regions with endemic malaria and people from such regions are usually carriers of the trait. Around 10% of Sickle Disease patients die by the age of 1 year and in many sub-Saharan countries, mortality is even higher. In sickle cell disease (SCD), the vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischaemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. The most significant risk factors of thromboembolism are the inherited genetic mutations in factor V Leiden (FVL) and prothrombin genes. This study comprised of 25 sickle cell disease patients and 25 healthy controls from Mulago Sickle Cell Clinic and Nakasero blood bank respectively. Genotyping was done using restriction fragment length polymorphism PCR for detection of FVL G1691A and Prothrombin G20210A gene mutations. There was a higher frequency of FVL G1691A mutations in SCD patients than in controls that is, 20/25 (80.0%) against 17/25 (68.0%) respectively. The relationship between FVL mutation and SCD was statistically insignificant as per chi-square test (X2 = 0.936, p>0.05, df = 1). Hence, there was no relationship between G1691A mutation and SCD in the study. Prothrombin G20210A gene mutation findings were entirely of the wild type GG genotype in both SCD patients and controls. Given the absence of any mutants in the study population, the chi-square test showed statistical insignificance for the relationship between G20210A mutation and SCD patients (df = 1; X2 = 0.0, p>0.05). FVL mutation results were inconclusive due to a small sample size used in the study. Therefore, there is need for more screening for FVL G1691A and prothrombin G20210A mutations for proper management of thrombotic complications that result into vascular occlusion in SCD patients. More research using larger sample sizes should be implemented for a higher degree of accuracy.