The methylene tetrahydrofolate reductase (C677T) mutation as a potential risk factor for avascular necrosis in sickle cell disease

Avascular necrosis (AVN) of the humeral and femoral heads is a frequent and debilitating complication of sickle cell disease. Some of the risk factors for AVN are alpha -thalassemia and age. Recently, newly discovered thrombo philia mutations have been associated with AVN in patients without sickle c ell disease. We studied the frequency of the thermolabile methylene tetrahy drofolate reductase (MTHFR) variant (C677T) in adult sickle cell patients w ith and without AVN. The frequency of the MTHFR mutation was 35.6% in patie nts with AVN and 12.9% in those without AVN (p = 0.006). These data suggest that the thermolabile MTHFR variant may be a contributing risk factor for AVN in some populations with sickle cell disease.