Zuntar I, Kalanj-Bognar S, Topić E, Petlevski R, Stefanović M, Demarin V. The glutathione S-transferase polymorphisms in a control population and in Alzheimer's disease patients. Clin Chem Lab Med. 2004 Mar;42(3):334-9.

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.

Bognar SK, Furac I, Kubat M, Cosović C, Demarin V. Croatian population data for arylsulfatase a pseudodeficiency-associated mutations in healthy subjects, and in patients with Alzheimer-type dementia and Down syndrome. Arch Med Res. 2002 Sep-Oct;33(5):473-7.

BACKGROUND: Arylsulfatase A (ASA) is a lysosomal enzyme involved in catabolism of cerebroside sulfate, whose deficiency causes metachromatic leukodystrophy, a rare autosomal recessive disorder characterized by storage of cerebroside sulfate, mainly in the nervous system. Low ASA activities have also been reported in healthy individuals and several neuropsychiatric disorders due to the condition termed ASA pseudodeficiency. The aim of this study was to establish frequency of two mutations associated with ASA pseudodeficiency in healthy individuals in the Croatian population as well as in persons with Alzheimer-type dementia and Down syndrome. METHODS: Presence of N350S and 1524+95 A-->G pseudodeficiency mutations was detected in genomic DNA extracted from leukocytes of healthy subjects (n = 125) and of patients with Alzheimer-type dementia (n = 18) and Down syndrome (n = 21). Arylsulfatase A activity was measured in leukocyte homogenates by spectrophotometry (lambda = 515 nm) using p-nitrocatechol sulfate as chromogenic substrate. RESULTS: Frequency of N350S mutation and mutation 1524+95 A-->G was estimated at 6.8 and 2.8% for healthy controls, 11 and 5.5% for Alzheimer-type dementia, and 12 and 9.5% for Down syndrome, respectively. Arylsulfatase A activity was slightly but not significantly decreased in leukocytes derived from subjects with dementia and Down syndrome in comparison with age-matched control samples. CONCLUSIONS: Frequency of two mutations associated with ASA pseudodeficiency in the Croatian population is slightly below the range reported for other populations. Additionally, despite the proposed role of arylsulfatase A pseudodeficiency as one of the predisposing factors for neuropsychiatric disorders, our preliminary results did not show significantly higher frequencies of either mutation in Alzheimer-type dementia or Down syndrome.