Hagh-flox Mouse

HAGH, the hydroxyacylglutathione hydrolase gene, encodes glyoxalase 2 (Glo2), a protein belonging to the metallo-β-lactamase family [1]. Glo2 is the second enzyme of the glyoxalase system, responsible for the detoxification of the α-ketothaldehyde methylglyoxal in cells. The glyoxalase system, with Glo1 and Glo2, utilizes glutathione as a cofactor in eukaryotic cells, and is involved in processes related to oxidative stress [1].

A study on schizophrenia patients and healthy controls in a Japanese sample investigated common genetic variants in HAGH. The SNP rs11859266 in the intronic region of HAGH showed a nominally significant association with schizophrenia (p = 0.020), though it did not survive multiple testing (empirical p = 0.091). In males, rs11859266 and rs3743852 in HAGH showed significant associations with schizophrenia at allelic and genotype levels, with some persistence after multiple testing [2].

In conclusion, HAGH is crucial for the function of the glyoxalase system in detoxifying methylglyoxal. Genetic studies of HAGH, such as those in schizophrenia, help to understand its role in disease-related processes. These findings contribute to uncovering the relationship between the glyoxalase system and certain diseases, providing insights into potential disease mechanisms and possible therapeutic targets.