Several metabolic and lifestyle determinants of plasma SAM have been reported, including plasma methionine and choline (positive), smoking (negative), as well as polymorphisms of MAT1A in certain subgroups.4 Plasma SAM is also elevated in a variety of clinical conditions, including cardiovascular disease,19 Alzheimer's disease20 and liver disease.21 There are scant data in humans on the relationship of plasma SAH and SAM with tissue levels of these metabolites, which tend to be several orders of magnitude higher. The gene discussed is MAT1A; the disease is liver disorder.