engleski

Glutathione S-transferase P1 polymorphism and risk of Alzheimer's disease

Introduction. Alzheimer's disease (AD) is a neurodegenerative disorder of unknown etiology. Many chemicals can affect the nervous system and some of them require metabolic activation to induce their toxic effects, so that genetic polymorphisms that encode for defective forms of the detoxifying enzymes can further increase the risk of effects from exposure to neurotoxicants. Glutathione transferases (GSTs) are a multiple gene family of phase II enzymes that catalyse detoxifying endogenous reactions with glutathione and protect cellular macromolecules from damage caused by cytotoxic and carcinogenic agents. The pi class of GST (GSTP1) is known as the most ubiquitous and prevalent of the GST isoenzyme in non-hepatic tissues. The aim of the study was to determine the genotype distribution for the GSTP1 A313G exon 5 polymorphism in Croatian healthy subjects and to investigate the association between GSTP1 polymorphism and Alzheimer's disease. Materials and Methods. The A313G GSTP1 genotypes were determined by PCR-RFLP method in samples of healthy controls (n=180) and patients with Alzheimer's disease (n= 40). Clinical diagnosis of the Alzheimer's disease was confirmed through battery of neuropsychological and laboratory tests and radiology (computerized tomography). Results. Frequency of the GSTP1 polymorphism in the Croatian healthy subjects was in the range reported for other populations. Analysis showed 20% homozygous mutant (GG) genotype in AD patients and 8% in controls, 25% heterozygous (AG) genotype in patients and 46% in controls, while wild type (AA) genotype was detected in 55% of patients and 46% of controls. There was statistically significant difference between AD patients and controls in the distribution of the GSTP1 exon 5 polymorphism (p=0.019). Additionally, there was statistically significant increase in Alzheimer's disease risk (OD=2.964, CI=1.149-7.646) for homozygous mutant (GG) genotype. Conclusion. Our preliminary results demonstrate that the GSTP1 A313G exon 5 polymorphism is associated with Alzheimer's disease risk.

glutathione-S-transferase P1 polymorphism; Alzheimer's disease

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