Clopidogrel resistance ... (Clopidogrel resistance) - Gen CYP2C19.

Clopidogrel resistance is a condition wherein the antiplatelet agent clopidogrel (Plavix) is less effective than normal to treat some patients. This medicine is given to prevent blood clots in patients with a history of stroke, heart disease, deep vein thrombosis or atherosclerosis. People with clopidogrel resistance to being administered the drug are at risk of serious complications which can be fatal. These people may have other coronary vascular event, a stroke, or thrombosis in a patient with coronary stents.

People with clopidogrel resistance can be divided into two categories: intermediate metabolizers and poor metabolizers. The intermediate metabolizers are able to process a clopidogrel, so partially benefit from administration, but are not protected completamiente of clot formation. Meanwhile, processed poor metabolizers of clopidogrel little or nothing, so the treatment effect is very limited and are at risk of forming a blood clot. Clopidogrel resistance appears to cause no health problems other than those related to the pharmacological treatment with this drug.

There are many genes involved in the conversion of clopidogrel to its active form and in determining drug effects in the body. CYP2C19 gene, located on the long arm of chromosome 10 (10q24) is particularly important for activation of clopidogrel, and some polymorphisms in this gene have been associated with clopidogrel resistance. CYP2C19 gene polymorphisms represent most of the variations in activation of clopidogrel due to genetic factors. Polymorphisms in genes other probably have minor effects on the activation of clopidogrel.

CYP2C19 gene encodes an enzyme found primarily in the liver cells, concfretamente activity is in the endoplasmic reticulum, involved in the processing and transport of proteins. CYP2C19 plays a role in processing of many drugs, including clopidogrel. This enzyme helps convert clopidogrel to its active form, which is required for the drug to perform its function in the body. In its active form, clopidogrel inhibits the function of the receptor protein P2RY12 located on the platelet surface. During clot formation, P2RY12 receptor protein helps platelets together to form a clot in order to close the damaged blood vessels and prevent blood loss. By inhibiting the receptor function P2RY12, clopidogrel reduces the formation of blood clots, including clots may cause heart problems, stroke and deep vein thrombosis.

The two gene polymorphisms CYP2C19 frequently associated with clopidogrel resistance (CYP2C19 * 2 and CYP2C19 * 3) result encoding a functional CYP2C19 enzyme which can not convert clopidogrel to its active form. Consequently, P2RY12 receiver continues to promote platelet aggregation and blood clots, which can lead wings coronary disorders, stroke and thrombosis in individuals with a history of these conditions. In addition to changes in specific genes, many other factors such as sex, age, weight, diet and other drugs play an important role in the body's response to clopidogrel.

Clopidogrel resistance is inherited in an autosomal codominant. Codominance means that two different versions of the gene are expressed, and both versions influence the genetic trait. Some people with clopidogrel resistance are reduced to convert the drug in its active form due to a polymorphism in a copy of the CYP2C19 gene resulting in a decrease in enzyme activity capacity. These individuals are described as intermediate metabolizers. Other individuals with clopidogrel resistance make little or no drug in its active form due to polymorphisms in both copies of the CYP2C19 gene, which results in a lack of enzyme activity. These individuals are described as poor metabolizers. It is important to note that not all individuals with mutations in the CYP2C19 gene are resistant to clopidogrel. These people who are at increased risk of developing resistance to clopidogrel may or may not have a bad reaction when treated with the drug.

Tests in IVAMI: in IVAMI perform detection of mutations associated with resistance to clopidogrel, by complete PCR amplification of exons in the CYP2C19 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).