GSTM1 copy number variation in the context of single nucleotide polymorphisms in the human GSTM cluster

Andrey V. Khrunin, Irina N. Filippova, Aydar M. Aliev, Tat’yana V. Tupitsina, Petr A. Slominsky, Svetlana A. Limborska

GSTM1 gene deletion is one of the most known copy number polymorphisms in human genome. It is most likely caused by homologous recombination between the repeats flanking the gene. However, taking into account that the deletion has no crucial effects on human well-being, and the ability of other GSTMs to compensate for the lack of GSTM1, a role for additional factors affecting GSTM1 deletion can be proposed. Our goal was to explore the relationships between GSTM1 deletion polymorphism and single nucleotide polymorphisms (SNPs) in the region of the GSTM cluster that includes GSTM2, GSTM3, GSTM4, and GSTM5 in addition to GSTM1. Real-time polymerase chain reaction was used to quantify the number of GSTM1 copies. Fourteen SNPs from the region were tested and their allelic patterns were compared in groups of Russian individuals subdivided according to their GSTM1 deletion genotypes. Linkage disequilibrium-based haplotype analysis showed substantial differences of haplotype frequencies between the groups, especially between individuals with homozygous GSTM1 -/- and +/+ genotypes. Exploration of the results of phasing of GSTM1 and SNP genotypes revealed unequal segregation of GSTM1 + and - alleles at different haplotypes. The observed differences in haplotype patterns suggest the potential role of genetic context in GSTM1 deletion frequency (appearance) and in the determination of the deletion-related effects.