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Aspirin intolerance: role of your DNA

Aspirin is the most commonly used countertop drug to reduce pain, fever, and inflammation. It is also used to treat or prevent heart attacks and chest pain. But Aspirin is not suited to everyone. Many develop allergies to Aspirin, which range from mild to severe rash and hives (Urticaria), nasal polyps, headache, swelling in the throat, runny nose, asthma, and in some cases life-threatening anaphylaxis reactions. While the occurrence and extent of Aspirin intolerance are widely established, the exact mechanism has not been identified so far.

Aspirin (acetyl salicylic acid) belongs to a class of drugs called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), which include other pain relieving medications such as Advil, Aleve etc. When you take Aspirin, a number of your body enzymes act on it in a multi-step manner until it is cleared from the body. Every person differs in the efficiency with which these enzymes perform. Enzymes are proteins that are encoded by DNA, and polymorphisms in DNA encoding these enzymes affect their activity. Genetic polymorphisms in Aspirin-metabolizing enzymes may be responsible for the wide-range of Aspirin intolerance.

A 2011 study in Korea investigated if genetic polymorphisms in Aspirin-metabolizing enzymes are linked to Aspirin-intolerance, specifically urticaria1. Aspirin is metabolized by three key enzymes, UDP-glucuronosyltransferase 1A6 (UGT1A6), cytochrome P450 2C9 (CYP2C9), and N-acetyl transferase 2 (NAT2). Each of these enzymes is known to have genetic polymorphisms. This study included 148 patients identified with Aspirin-intolerant urticaria (AIU) and 260 normal healthy control subjects (NC) with no family history of Aspirin allergy. They investigated the DNA of these two groups for the nine polymorphisms among the three enzymes and identified a significant association of a polymorphism in CYP2C9 (-1188T>C) with the Aspirin sensitivity phenotype. What this means is, healthy individuals have the nucleotide T at position 1188 of DNA coding for CYP2C9, while patients with Aspirin sensitivity have a higher propensity to carry the nucleotide C at this position. No significant association was found with the other two enzymes, UGT1A6 and NAT2. Further studies are required to determine how this variation affects the function of the CYP2C9 enzyme in Aspirin metabolism.

CYP2C9 is an important enzyme involved in the metabolism and clearance of NSAIDs as well as many other therapeutic drugs, and genetic polymorphisms in this enzyme have been known to be associated with drug efficiency and tolerance. So knowing your genetic makeup for CYP2C9 can help in pre-determining if these drugs are suitable for you. This can be done using pharmacogenetic tests such as Pillcheck, which will screen your DNA for polymorphisms in a variety of enzymes involved in drug metabolism, including for CYP2C9.

  1. Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy Asthma Immunol Res. 2011 Oct;3(4):273-6
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