Correlation of the C677T MTHFR genotype with homocysteine levels in children with sickle cell disease

Recently, a mild to moderate elevation in the plasma homocysteine (Hcy) level has been found to be an important risk factor for stroke. Homozygosity for a common mutation (C677T) in the gene encoding for the enzyme methylenetetrahydrofolate reductase (MTHFR) involved in Hcy metabolism has been associated with increased levels of Hey. To determine the role of hyperhomocysteinemia in the pathogenesis of stroke in children with sickle cell disease (SCD), Hey levels and C677T MTHFR genotype were determined in 40 patients homozygous for hemoglobin SS and compared with 197 healthy children. Eleven of 40 patients with SCD had a history of stroke. The prevalence of homozygosity for the C677T MTHFR variant was 5% in the patients with SCD. The median Hey level was 5.8 mu mol/L in the patients versus 5.4 mu mol/L in the controls (Fisher's, P > 0.05). There was no correlation of Hey levels with the MTHFR genotype in patients with SCD. In patients with SCD and stroke, the median Hey level was 4.8 mu mol/L versus 6.0 mu mol/L in those without stroke (P = 0.44, Mann-Whitney rank sum test). There was no difference in the proportion of patients with SCD with or without stroke who were homozygous for the C677T MTHFR mutation (0/11 versus 2/29; Fisher's, P = 1.000). In conclusion, this study failed to demonstrate an elevation in plasma Hey levels in children with SCD compared with normal controls. Furthermore, hyperhomocysteinemia did not seem to be a significant factor in the pathogenesis of stroke in children with SCD.