Determination of variations of the primary structure of the UGT1A1, DPYD, GSTP1, and ABCB1 genes involved in the metabolism of antitumor agents

Abstract

A individual approach to the treatment of cancer patients, which takes the genetic features of the patient’s metabolism into account, allows one to choose an appropriate drug and its dose, that increases the efficiency of therapy and prevents the development of side toxic effects. For this purpose, we developed a biological microarray-based method for studying the primary structure of patient DNA and identifying polymorphisms in the UGT1A1, DPYD, GSTP1, and ABCB1 genes associated with alterations in xenobiotic metabolism. Genotyping of samples from 89 cancer patients and 15 healthy donors was carried out using the developed microarray. The results of determination of the primary structure of DNA samples coincided completely with the control sequencing. To increase the specificity of determination of polymorphic variants of the UGT1A1 gene, we used hybridization probes containing LNA nucleotides. The frequencies of polymorphic allelic variants of the UGT1A1*28, DPYD*2A, GSTP1 (I105V), and ABCB1 (C3435T) genes in the studied sample were 0.39, 0, 0.33, and 0.57, respectively.