MTHFR and hyperhomocysteinemia: The most extensively studied variant in MTHFR gene is the polymorphism MTHFR g.677C>T (rs1801133), which changes an alanine to valine in aminoacid 222 (p.A222V) in the enzyme regulatory domain and causes a thermolabile enzyme with decreased activity at 37°C and so hyperhomocysteinemia [40–43].