[Molecular genetics of cardiovascular diseases]

This review introduces recent progress in molecular genetics of cardiovascular diseases. Many genes and their mutations causing familial cardiovascular diseases have been discovered, including familial hypertrophic cardiomyopathy which is caused by mutated cardiac beta myosin heavy chain, light chains, troponin T, troponin I, or alpha-tropomyosin, and long QT syndrome by KvLQT1, HERG, minK or cardiac voltage-dependent Na channel mutation. The mutations in causative genes can affect clinical courses of diseases; amino acid substitutions of cardiac beta myosin heavy chain with charge changes seem to cause poorer prognosis of hypertrophic cardiomyopathy. Besides monogenic diseases, there are many cardiovascular diseases affected with genetic polymorphisms, such as hypertension, ischemic heart disease and atherosclerosis. Specific amino acid mutations or polymorphisms in the promoter region of the genes are known to become a risk factor of these diseases. Polymorphisms of genes encoding apolipoprotein E, angiotensin converting enzyme, angiotensinogen and endothelial NO synthase (ecNOS) have been well characterized as an important risk factor of cardiovascular diseases. We recently found a novel gene which seems to affect human aging phenotype and vascular endothelial function. It is important as a future study to clarify the regulatory mechanisms of the klotho gene in the cardiovascular system and the clinical significance of klotho gene polymorphisms.