Screening for inter-individual splicing differences in human GSTM4 and the discovery of a single nucleotide substitution related to the tandem skipping of two exons

Abstract

The glutathione S-transferase Mu class (GSTM) genes encode phase II metabolism enzymes that are involved in the detoxification of various carcinogens and drugs. Some genetic polymorphisms in GSTM genes are related to disease phenotypes and drug-metabolism differences in the population. Polymorphisms that alter gene-splicing patterns are functionally very important because they often lead to the insertion or deletion of many amino acids. To identify inter-individual differences in the splicing pattern of the GSTM4 gene, we used reverse transcriptase polymerase chain reaction (RT-PCR) to screen cDNA from 96 human liver samples. We discovered a novel splice variant of GSTM4 that resulted from tandem skipping of exons 4 and 5. This exon-skipping event is associated with a mutation at the splice acceptor site in intron 4.