Functional polymorphisms in genes relevant to homocysteine metabolism (e.g., 5,10-methylenetetrahydrofolate reductase; MTHFR and glutamate carboxypepidase II; GCPII [59]–[61]) that result in accumulation of SAH likely augment the effects of APS and HPS haplotypes. This evidence concerns the gene MTHFR and autoimmune polyendocrinopathy.