GENETIC AND NONGENETIC FACTORS FOR MODERATE HYPERHOMOCYST(E)INEMIA

To assess the risk for homocyst(e)ine-associated vascular disease, ove rt hyperhomocyst(e)inemia should be demonstrated. In nonhomocystinuric subjects, clinical vascular disease must have developed after 40 or m ore years of persistent hyperhomocyst(e)inemia which may not be presen t without a genetic defect(s). Nongenetic factors, however, may amplif y or mask phenotypic expression of a genetic defect, causing difficult ies for the evaluation of hyperhomocyst(e)inemia based on plasma homoc yst(e)ine concentration alone. Therefore, the search for genetic defec ts seems as important as the determination of plasma homocyst(e)ine co ncentration in evaluating the relationship between hyperhomocyst(e)ine mia and the development of vascular disease. If genetic defect, such a s heterozygous cystathionine synthase deficiency or thermolabile methy lenetetrahydrofolate reductase is not detected, post-methionine homocy st(e)ine determination is a suitable means to identify genetic suscept ibility to hyperhomocyst(e)inemia when the environmental factors are s imilar in the control and study groups.