Aspirin Resistance: An Emerging Clinical Predicament is Associated with Single Nucleotide Polymorphisms

摘要

People use prescribed drugs all the time and there are different responses to a particular drug shown by different individuals. These responses largely have to do with single nucleotide polymorphisms. Aspirin is a salicylate drug often used as an analgesic, antipyretic, anti-inflammatory medication. It also has an anti-platelet effect by inhibiting the production of thromboxane. Approximately 40, 000 tones of this drug is being consumed every year. However, there are individual variations in response to aspirin, creating the term “aspirin non- responsiveness” or “aspirin resistance”. Aspirin and _ its interaction with platelet aggregation inhibitor pathway genes (forty nine genes involved) were studied to hit upon the gene mutations, which gave rise to different responses to the same drug. Twelve of these exon mutations changed the originally coded amino acid with a new one (PTGDR, ITGB3, P2RY12, PLA2G4A, PLA2G4B, VWF, PTGS1, TBXAS1, TBX2R2, F2, F2RL3, and GNAI3). These polymorphisms lie in the extracellular, cytoplasmic, signal sequence and transmembrane domains of the protein, a-helical regions and B-pleated sheets. These are significant pertaining to the transformation in polarity and charge of the amino acid side chains that in turn modify their interactions with other amino acid residues and aqueous surroundings. This alters the normal functioning of the genes and finally leads to differential responses to the drug aspirin.