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Abstract
Metabolism of valproic acid, a widely used drug, is only partially understood. It is mainly metabolized through glucuronidation and acts as a substrate for various UDP-glucuronosyltransferases (UGTs). UGTs metabolizing valproic acid in the liver are UGT1A3, UGT1A4, UGT1A6, UGT1A9 and UGT2B7, with UGT1A6 and UGT2B7 being the most prominent. Polymorphisms in genes expressing these enzymes may have clinical consequences, regarding dosing, blood levels of the drug and adverse reactions. Not all genes are well studied and studies, where they exist, report conflicting results. Prevalence of polymorphisms and various haplotypes is also of great importance, as it may suggest different therapeutic approaches in various populations. Presented here is a review of currently known polymorphisms, their functional impact, when known, and their prevalence in different populations, highlighting the current state of understanding and areas where there is a lack of data and suggesting new perspectives for further research.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.