Homocysteine and MTHFR Mutations

Abstract

Homocysteine is a chemical in the blood that is produced when an amino acid (a building block of protein) called methionine is broken down in the body. We all have some homocysteine in our blood. Elevated homocysteine levels (also called hyperhomocysteinemia) may cause irritation of the blood vessels. Elevated levels of homocysteine show an increased risk for (1) hardening of the arteries (atherosclerosis), which could eventually result in a heart attack and/or stroke, and (2) blood clots in the veins, referred to as venous thrombosis. The purpose of this Cardiology Patient Page is to explain the relation between elevated homocysteine levels and blood clots in the arteries and veins; to discuss the causes of elevated homocysteine levels, including common genetic variants in the MTHFR gene (see the “What Do I Need to Know About a Hereditary Predisposition?” section); and to describe ways to monitor and lower homocysteine levels to possibly improve health. In 1962, it was reported that people with a rare genetic condition called homocystinuria were prone to develop severe cardiovascular disease in their teens and 20s. In this condition, a defective enzyme causes an accumulation of homocysteine in the blood, resulting in very high levels. Studies of children with homocystinuria led to the discovery that elevated homocysteine levels are a risk factor for developing atherosclerosis and blood clots in the arteries and veins. Although homocystinuria is a rare disease (affecting about 1 in 200 000 people), many more people have mildly or moderately elevated homocysteine levels. Some people have elevated homocysteine levels (Table 1) caused by a deficiency of B vitamins and folate in their diets. High homocysteine levels are also seen in people with kidney disease, low levels of thyroid hormones, psoriasis, and with certain medications (such as antiepileptic drugs and methotrexate).1 It has been recognized …