engleski

Association between glutathione s-transferase P1 polymorphisms and Alzheimer's disease risk

Glutathione S-transferases (GSTs) catalyze the conjugation of glutathione to numerous potentially genotoxic compounds. 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. 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 and C341T exon 6 polymorphisms in Croatian healthy subjects and to investigate the association between GSTP1 polymorphism and Alzheimer's disease. The A313G and C341T GSTP1 genotypes were determined by PCR-RFLP method in samples of healthy controls (n=231) and patients with Alzheimer's disease (n=56). Clinical diagnosis of the Alzheimer's disease was confirmed through battery of neuropsychological and laboratory tests and radiology (computerized tomography). There were no statistically significant differences between AD cases and controls in the distribution of A313G and C341T genotypes. However, the frequencies of the mutant genotypes were higher in AD patients (13% for both A313G and C341T) when compared with control subjects (7% for A313G and 8% for C341T), which indicated that GSTP1 GG genotype could be associated with a 2-fold risk and GSTP1 TT genotype with a 1.7-fold risk of AD. The frequencies of GSTP1 alleles (A, B, C, D) were estimated as follows: 52.7%, 15.2%, 12.5% and 19.6% for AD cases and 58.4% 14.1% 14.1% and 13.4% for controls, showing higher frequency of allele D in AD when compared with controls. Finally, the estimation of GSTP1 haplotypes distribution and frequencies indicated a potentially important association of GSTP1*A/GSTP1*B and GSTP1*A/GSTP1*C haplotypes with reduced risk, and of GSTP1*B/GSTP1*B and GSTP1*C/GSTP1*D haplotypes with higher risk for Alzheimer's disease.

GSTP1; PCR-RFLP; polimorphisms; Alzheimer's disease

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