Genetic and nongenetic factors for moderate hyperhomocyst(e)inemia

To assess the risk for homocyst(e)ine-associated vascular disease, overt hyperhomocyst(e)inemia should be demonstrated. In nonhomocystinuric subjects, clinical vascular disease must have developed after 40 or more years of persistent hyperhomocyst(e)inemia which may not be present without a genetic defect(s). Nongenetic factors, however, may amplify or mask phenotypic expression of a genetic defect, causing difficulties for the evaluation of hyperhomocyst(e)inemia based on plasma homocyst(e)ine concentration alone. Therefore, the search for genetic defects seems as important as the determination of plasma homocyst(e)ine concentration in evaluating the relationship between hyperhomocyst(e)inemia and the development of vascular disease. If genetic defect, such as heterozygous cystathionine synthase deficiency or thermolabile methylenetetrahydrofolate reductase is not detected, post-methionine homocyst(e)ine determination is a suitable means to identify genetic susceptibility to hyperhomocyst(e)inemia when the environmental factors are similar in the control and study groups.