Role of homocysteine in complex disorders

Abstract

Homocysteine, a thiol amino acid, is present at a branch point in the methionine metabolism. The intracellular homocysteine metabolism is well regulated and its concentration in circulation is less than 12 μmol/L. However, improper metabolism of homocysteine due to genetic and/or environmental factors (including diet) may result in high plasma homocysteine levels. An elevated level of homocysteine (hyperhomocysteinemia) has been associated with various diseases and/or clinical conditions. It has also been implicated as an independent risk factor for cardiovascular disorders. Further, hyperhomocysteinemia has been found to have graded effect on the risk of coronary artery disease (CAD) and the extent and severity of the disease. In CAD patients, homocysteine levels are a significant predictor of mortality, independent of traditional risk factors. CAD is one of the cardiovascular diseases that is probably the largest cause of mortality and morbidity worldwide and is reaching epidemic proportions in developing countries. It has been predicted that deaths due to CAD is likely to be more than any other disease in India. Furthermore, in Indians, CAD tends to occur much earlier than any other ethnic groups. This is surprising considering the fact that a majority of Indian population adheres to a vegetarian diet which is supposed to be a healthier alternative especially in the context of cardiovascular disorders. However, vegetarian diet lacks important micronutrient like vitamin B12 and thus it can be presumed that vegetarians have low levels of vitamin B12, an important micronutrient, and as a consequence elevated homocysteine levels. Apart from the nutritional factors, many single nucleotide polymorphisms (SNP) especially those present in the genes involved in the homocysteine metabolism have been shown to be associated with the altered levels of homocysteine.