SERPINE1 and hyperhomocysteinemia: However, sport activity directly modifies other genetic effects on vagus reactivity by increasing it in non-C allele carriers of the MTHFR gene and in 5G-allele carriers of the PAI-1 gene, most likely through epigenetic mechanisms, which may heighten the pro-coagulation bias determined by hyperhomocysteinemia in the former group of subjects39, but compensate for the coagulation deficit in the latter group of subjects40, 41.