Peer-reviewed veterinary case report
Low expression GSTT1 gene variant linked to lymphoma risk in golden
By Craft, S et al.·Published in Veterinary and comparative oncology·2018·Department of Medical Sciences·View original on PubMed →
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Original publication title: Characterization of a low expression haplotype in canine glutathione S-transferase (GSTT1) and its prevalence in golden retrievers.
- Species:
- dog
Plain-English summary
A study found that a specific genetic variant in golden retrievers may lower the expression of an important detoxification enzyme, which could affect their ability to handle carcinogens. This variant was present in some golden retrievers with lymphoma but not in healthy ones. However, the researchers concluded that this genetic change does not appear to be a significant risk factor for developing lymphoma in golden retrievers. Therefore, while this variant may reduce enzyme levels, it doesn't seem to increase the likelihood of cancer in these dogs.
People also search for: golden retriever lymphoma risk factors · dog cancer genetics · golden retriever health issues
Abstract
Glutathione S-transferase-theta (GSTT1) is a carcinogen detoxification enzyme, and low activity variants are associated with lymphoma in humans. We recently found a variant in the 3' untranslated region (UTR) of canine GSTT1, *101_102insT, which was predicted to change miRNA binding and was found in 5 of 17 golden retriever (GR) dogs with lymphoma but none of 14 healthy GRs. The aim of this study was to determine whether this variant led to decreased GSTT1 expression and was a discernible risk factor for lymphoma within the GR breed. On resequencing, *101_102insT appeared to be in complete linkage disequilibrium with 3 additional 3'UTR variants, leading to the inferred haplotype *3T>C; *101_102insT; *190C>A; *203T>C. In canine livers that were heterozygous for this variant haplotype, GSTT1 protein expression was significantly lower compared to the reference haplotype (densitometry .40 vs .64, P = .022), and GSTT1 transcript levels by qPCR were also significantly lower (fold difference .52, P = .012), without evidence of substantial allelic expression imbalance. The variant haplotype led to >50% decrease in expression in vitro (.31 ± .07 vs .64 ± .19; P = .019). We found no significant difference in minor allele frequencies between 71 GR dogs with lymphoma (MAF .162) and 33 healthy age-matched controls (MAF .136, P = .69). Our results indicate that the variant GSTT1 3'UTR haplotype containing *101_102insT reduces gene expression, which could lead to impaired carcinogen detoxification, but was not a detectable risk factor for lymphoma in GR dogs.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/28840668/