While much evidence has been provided supporting the involvement of FV Leiden [100,101,102,103], deficiencies in protein C and/or S [114,115], APCR [115,116] and high FVIII levels [162,163,164,165] in the pathogenesis of ONFH and ONK, other hereditary anomalies of coagulation possibly have no influence (e.g., the 20210A polymorphism in the prothrombin gene [100,101,119,120]) or show contradictory results (e.g., the MTHFR C677T gene polymorphism [102,119,120,124,125,126]) in relation to the osteonecrosis of large joints. The gene discussed is MTHFR; the disease is osteonecrosis.