MTHFR and myocardial ischemia: The studies exclude confounding, as generally understood, because the raised homocysteine concentrations occur as a result of a genetic mutation randomly distributed across the population; people with and without the mutation would not in expectation differ in other cardiovascular risk factors and direct observation has shown that they do not.[3] Genetic confounding is theoretically possible if there were a gene linked to the MTHFR polymorphism that also increases serum homocysteine and IHD risk.