Thrombophilic mutations and risk of vascular complications in sickle cell disease

Abstract

IntroductionSickle cell disease (SCD) is an inherited hemoglobinopathy that is characterized by hemolysis and hypercoagulability. The coinheritance of genetic variants causing thrombophilia may aggravate the hypercoagulable state in SCD patients. The identification of SCD patients with the risk factors for developing thrombosis may play an important role in the prevention and management of vaso-occlusive crises (VOCs) and vascular complications in these patients. The objective of the current case control study was to determine the relationship between thrombophilic variants, methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden (FVLG1691A), prothrombin gene (PRT) G20210A variants and susceptibility to VOCs and vascular complications in Egyptian SCD patients. Patients and methodsEighty two patients (53 SS, 29 S/β thalassemia) and 70 healthy individuals were genotyped for these thrombophilic variants using PCR-RFLP. Sanger sequencing and real time PCR-based SNP genotyping assay were done for positive cases. ResultsMTHFR C677T was found in 40.2% of cases in heterozygous state (43.4% of SS, 34.5% of S/β thalassemia) with a highly significant difference in the prevalence between cases and healthy subjects (P = 0.001). Heterozygous FVLG1691A mutation was found in 13.4% of cases (15.1% of SS, 10.3% of S/β thalassemia). Seven cases carried both FVLG1691A and MTHFR C677T variants. There was a statistical significant difference between the frequency of acute painful crises and the heterozygosity for MTHFR C677T and FVLG1691A variants (P = 0.003). The heterozygote state of PRT G20210A mutation was present in one SS patient. ConclusionOur data suggested that the MTHFR C677T and FVLG1691A variants have a high impact as risk factors for VOCs in SCD.