Mini-Review on the Implications of Gene Polymorphism in the Metabolism of Xenobiotics

Abstract

One of the most common medical issues in children and adults is accidental poisonings ranging from medicines to toxic substances such as alcohol and toluene and even metals like iron and lead. The way these substances are metabolised depends on a plethora of factors such as age, sex and even ethnicity. Besides these factors, there is one that holds an even more significant weight on how substances are metabolised -genes, or more precisely, alleles of specific genes. In recent years, genetic studies have significantly increased in number, and more and more genetic polymorphisms are being discovered and studied for their different effects compared to wild types. We performed a literature search on the subject comprising studies focusing on the most common substances in intoxications, as well as polymorphisms of CYP450 isoenzymes, HLA system and others. We obtained various studies on the subject highlighting differences in expression depending on the present allele, with some having diametral opposed effects while others being null. Thorough knowledge of these complex mechanisms is an important first step towards the development of tests to detect susceptibility to severe side effects and towards rapidly customising the therapeutic approach. RezumatUn aspect clinic sensibil, la copii și adulți, este otrăvirea accidentală cu diverse substanțe, de la medicamente la substanțe toxice cum ar fi alcoolul, toluenul sau chiar metale ca fierul și plumbul. Modul în care aceste substanțe sunt metabolizate este dependent de o varietate de factori cum ar fi vârsta, sexul sau etnia. Pe lângă aceștia, factorii genetici își pun amprenta considerabil asupra metabolismului substanțelor, fiind descoperite din ce în ce mai multe polimorfisme genetice. În acest studiu am analizat date din literatura de specialitate care se concentrează pe cele mai comune intoxicații, precum și diferite polimorfisme genetice. Aprofundarea acestor mecanisme complexe reprezintă un prim pas spre dezvoltarea de teste capabile să detecteze susceptibilitatea individuală la diferite substanțe, precum și personalizarea terapiilor.