Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

Abstract

BACKGROUND: Homocysteinemia is regarded as potential predictor for vaso-occlusive phenomenon often observed in sickle cell hemoglobinopathy. The objective was to determine the relationship of these genotypes with homocysteinemia and the predictive coefficient of these polymorphisms on the vascular-related crisis in the presence of sickle cell gene. MATERIALS AND METHODS: The case-control study comprised 89 children diagnosed with sickle disease with features of vascular crisis, 160 children without crisis and 252 apparently healthy children as the control group. The genotypes were assayed for C677T and A1298C variants and their association and predictor effect for homocysteinemia of different grades were analyzed. Sequential multiple regression model was used to assess the predictive effect. RESULTS: Homocysteine levels were significantly higher in the crisis group (P < 0.001). When compared to the wild genotype the variants depicted significantly raised homocysteine levels (P < 0.001). The prevalence of C677T was 29.9% and that for A1298 was 66.3% in the study population. The odds for crisis was 2.3 times for crisis in TT677 and 1.34 times in CC1298 variants. The genotypes revealed a significant association with different grades of homocysteinemia (P < 0.001). Plasma homocysteine depicted significant negative correlation with weight, height, body mass index and hemoglobin levels. None of the TT variants reported normal homocysteine values. Shift toward the variant form showed an increase of homocysteine levels by 7.3 units and 6.9 units for C677T and A1298C single-nucleotide polymorphisms respectively. CONCLUSION: Co-presence of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms could be important predictor for homocysteinemia and thus contribute toward vascular crisis in sickle cell patients.