Stevens-Johnson syndrome: relation with phenytoin and carbamazepine associated with HLA and CYP polymorphism in Colombia

Abstract

The genetic polymorphisms of the Human Leukocyte Antigens (HLA) and Cytochromes P450 (CYP) CYP2C19 and CYP2C9 have been proposed as key elements for susceptibility to antiepileptic drugs such as Phenytoin (PHT) and Carbamazepine (CBZ). These hepatic isoenzymes and HLA´s exhibit genetic polymorphism with interindividual variability in catalytic activity. Stevens-Johnson Syndrome (SJS) is one of the idiosyncratic adverse effects related to PHT and CBZ. The aim of this work is to relate the polymorphisms of the HLA and CYP alleles with the Stevens- Johnson syndrome caused by phenytoin and carbamazepine in the Amerindian population of Colombia. Methodology: A systematic search was carried out in Clinical Key, Pro Quest and PubMed, the results were tabulated and organized according to their expression to be analyzed by means of the MEGA7 software, using Allele Frequencies to know the allelic frequency of HLA in the Colombian Amerindian population. Results: It was found that the increased risk of Stevens- Johnson syndrome by Phenytoin and Carbamazepine was significantly linked with HLA-A*23: 01, HLA-A*30: 01, HLA-A*30: 02, HLA-A*03:01, HLA-A*11: 01, HLA-A*26: 01, HLA-A*29: 02, HLA-A*68: 01, HLA-A*02: 01, HLA-A*02:22 relating HLA-B*15: 02 and HLA-B*51: 01 as a risk factor and HLA-A*24: 02 as a protective marker for SJS. In the population studied in this work, the presence of the alleles HLA-A*23:01, HLA-A*30:01, HLA-A*30:02, HLA-A*03:01, HLA-A*11:01, HLA-A*26:01, and HLA-A*24:02, like CYP2C9*3 and CYP2C19.