Plasma homocysteine and the genetics of cardiovascular disease.
Cardiovascular disease (CVD) is extremely complex. It results from the interaction of many genetic and environmental factors. Several studies have demonstrated its genetic basis, estimating a heritability of approximately 60%. In the last 5 years, at least 19 genome-wide explorations for genes related to CVD have been undertaken, but none has yet unequivocally demonstrated a causal relationship with the disease. One method that can be used to find the causative genes is analyzing intermediate genetic phenotypes or risk factors, such as plasma homocysteine (Hcy). A recent genome-wide quantitative-trait-linkage analysis of Hcy plasma levels has found a previously unsuspected gene as the major genetic determinant of this risk factor. It codes for the enzyme nicotinamide N-methyltransferase, and this gene is now a candidate gene that explains a portion of the genetic basis of CVD. If confirmed, this finding will probably influence future research on the mechanisms underlying atherosclerosis and CVD, as well as other complex diseases related to plasma Hcy levels, such as Alzheimer's disease and osteoporosis.
Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Sant Antoni M feminine Claret 167, 08025 Barcelona, Spain. jsouto@santpau.es
Juan Carlos
JC
Souto
José Manuel
JM
Soria