Nonsteroidal anti-inflammatory drugs are the medications most frequently involved in hypersensitivity reactions to drugs. These can be induced by specific immunological and nonimmunological mechanisms, being the latter the most frequent. The nonimmunological mechanism is related to an imbalance of inflammatory mediators, which is aggravated by the cyclooxygenase inhibition. Genetic studies suggest that multiples genes and additional mechanisms might be involved. The proposals of this review is summarize the contribution of variations in genes involved in the arachidonic acid, inflammatory and immune pathways as well as the recent genome-wide association studies findings related to cross-intolerant nonsteroidal anti-inflammatory drugs hypersensitivity reactions. In addition, using integration of different genetic studies, we propose new target genes. This will help to understand the underlying mechanism of these reactions.
Keywords: NECD; NERD; NIUA; NSAIDs hypersensitivity; aspirin intolerance; cross intolerant reactions; genetic association studies; mechanisms; selective reactions.