The glutathione S-transferase polymorphisms in a control population and in Alzheimer's disease patients.
In this study, we investigated the role of glutathione S-transferase P1 (GSTP1) polymorphisms in the pathogenesis of Alzheimer's disease (AD). We genotyped the GSTP1 polymorphisms in exon 5 (A313G) and exon 6 (C341T) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 56 Croatian patients with AD and 231 controls. Distributions and frequencies of GSTP1 genetic variants were not statistically different between AD patients and healthy controls. Higher frequencies of the mutant genotypes were observed in AD patients (13% for both A313G and C341T) when compared with control subjects (7% for A313G and 8% for C341T), but association of GSTP1 GG (OR 2.057, 95% CI 0.796-5.315, p=0.094) and TT (OR 1.691, 95% CI 0.669-4.270, p=0.514) genotypes with an increased risk of AD was not confirmed by statistical analysis. The frequencies of GSTP1 alleles (A, B, C, D) did not significantly differ between AD patients and controls and they were indicated 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. The estimation of the GSTP1 haplotype distribution showed that GSTP1*A/GSTP1*B and GSTP1*A/GSTP1*C haplotypes were less frequent, while GSTP1*B/GSTP1*B and GSTP1*C/GSTP1*D haplotypes were more frequent in AD patients than in controls. In conclusion, the involvement of GSTP1 alleles in individual susceptibility to AD was not confirmed as statistically significant in the tested Croatian Caucasian population. A possible role of GSTP1 in the complex etiopathogenesis of AD is further discussed, based on observed differences in haplotype distribution and higher frequencies of mutant genotypes in AD patients.
Zuntar
Irena
I
Department of Analytical Toxicology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. izuntar@pharma.hr
Kalanj-Bognar
Svjetlana
S
Topić
Elizabeta
E
Petlevski
Roberta
R
Stefanović
Mario
M
Demarin
Vida
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D002847:Chromatography, Agarose; D017523:Croatia / Q000453:epidemiology; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D005982:Glutathione Transferase