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Bucossi S.,Biomedical University of Rome | Polimanti R.,University of Rome Tor Vergata | Mariani S.,Biomedical University of Rome | Ventriglia M.,Biomedical University of Rome | And 7 more authors.
Journal of Alzheimer's Disease | Year: 2012

Copper homeostasis appears abnormal in Alzheimer's disease (AD) patients. The aim of this study was to assess whether loci of susceptibility for AD lie in the Wilson's disease (WD) ATP7B gene. We studied single nucleotide polymorphisms (SNPs) K832R (c.2495 A>G, rs1061472) and R952K (c. 2855 G>A, rs732774) of the WD gene in 251 AD patients and 201 healthy controls. We also evaluated their relation with apolipoprotein E (ApoE) ε4 allele frequency. R allele in K832R [adjusted Odds Ratio (OR) = 1.71 (1.12-2.60); p = 0.012] and the K allele in R952K [adjusted OR = 1.82 (1.19-2.80); p = 0.006] ATP7B SNPs were associated with an increased risk of developing AD, as well as the haplotype R832/K952, containing the 2 risk alleles (X 2 = 4.85; p = 0.028). Conversely, the K832/R952 haplotype appeared to confer protection against the disease (X 2 = 7.21; p = 0.007). No difference in the frequency of the ATP7B alleles between carriers and non-carriers of the ApoE ε4 variant was revealed. The linkage disequilibrium (LD) analysis revealed an association between K832R and R952K substitutions in both AD patients (D' = 0.79) and controls (D' = 0.81). A high LD between K832R and R952K was also confirmed in all HapMap populations. Our investigation demonstrated the presence of loci of susceptibility for AD in the WD ATP7B gene, supporting a role of copper dysfunction in contributing or accelerating neurodegenerative processes leading to AD. © 2012-IOS Press and the authors. All rights reserved. Source


Polimanti R.,University of Rome Tor Vergata | Polimanti R.,Clinical Physiopathology Center | Piacentini S.,University of Rome Tor Vergata | De Angelis F.,University of Rome Tor Vergata | And 2 more authors.
Disease Markers | Year: 2011

Over the last two decades, significant data has been accumulated linking Glutatione S-Transferases (GSTs) with the development of several diseases. Contemporary studies have demonstrated the impact of ethnicity on GST allele frequencies. The aim is to verify if the variability of GST genes reflects population demographic history or rather selective pressures. GST genes (GSTM1, GSTO1 GSTO2, GSTT1) were analysed in three Ecuadorian populations (Cayapas, n=114; Colorados, n=104; African-Ecuadorian, n=77) and compared with HapMap data. GST SNPs were determined using the PCR-RFLP method while GST null phenotype was determined using a Multiplex PCR. The population relationship achieved using GSTM1 positive/null, GSTO1*A140D, GSTO2*N142D and GSTT1 positive/null are in agreement with the data obtained using neutral polymorphisms: Amerindians are close to Asian populations and African-Ecuadorians to African populations. To what concerns GSTO1*del155 and GSTO1*K208 variants, allele frequencies never exceeded 10%, showing no significant differences in the Ecuadorian groups and in worldwide populations. The features of GSTO1*del155 and GSTO1*K208 variants and their association with arsenic biotransformation deficiency suggest the presence of a selection mechanism towards these loci. In particular, this hypothesis is strengthened by a possible linkage between these alleles and the susceptibility of arsenic-induced male infertility. © 2011 - IOS Press and the authors. All rights reserved. Source


Piacentini S.,University of Rome Tor Vergata | Polimanti R.,University of Rome Tor Vergata | Polimanti R.,Clinical Physiopathology Center | Porreca F.,University of Rome Tor Vergata | And 3 more authors.
Molecular Biology Reports | Year: 2011

Glutathione S-transferases (GSTs) are a superfamily of detoxificant enzymes. Pharmacogenomic studies have revealed interethnic differences in GST allelic frequencies. This study is focused on GSTT1 (gene deletion, rs17850155, rs2234953, and rs11550605) and GSTM1 (gene deletion) gene frequency distributions in two population samples of Europe origin (Italy, n = 120; Spain, n = 94) and two population samples of Africa origin (Cameroon, n = 126; Ethiopia, n = 153). Detection of GSTT1 and GSTM1 null genotypes was performed by multiplex PCR analysis, while the other GSTT1 gene polymorphisms were detected using allele specific PCR and sequencing. GSTT1 and GSTM1 null frequencies in the samples analyzed fit with the variability range observed in European and African populations, respectively. The SNP analysis in GSTT1 gene did not highlight any nucleotide substitution in 493 individuals analyzed. The comparisons among GSTM1 and GSTT1 null phenotype frequencies in worldwide populations show different patterns between Asians, Africans, and Europeans. Important insights into the effects of GSTM1 and GSTT1 gene deletions on the pathogenesis of human diseases have been hypothesized. Detailed studies on the geography of GST variants could therefore increase knowledge about the relationship between ethnicity and the prevalence of certain diseases. © 2010 Springer Science+Business Media B.V. Source


Polimanti R.,University of Rome Tor Vergata | Piacentini S.,University of Rome Tor Vergata | Moscatelli B.,Clinical Physiopathology Center | Pellicciotti L.,Clinical Physiopathology Center | And 2 more authors.
Clinical and Experimental Pharmacology and Physiology | Year: 2010

1. Previous studies have established that genetic alterations in glutathione S-transferase enzymes may change the ability of the airway to deal with toxic substances and increase the risk of asthma. The present study analysed the association between asthma and GSTA1, GSTO1 and GSTO2 gene polymorphisms. 2. The GSTA1*-69C/T, GSTO1*A140D and GSTO2*N142D polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism, whereas the GSTO1*E155del polymorphism was detected using the confronting two-pair primer method. 3. Distribution of the GSTA1*-69C/T genotype differed significantly between asthmatics and controls. Subjects with at least one allele -69T in the GSTA1 genotype have an increased risk of asthma (odds ratio (OR) 3.45; 95% confidence interval (CI) 1.80-6.62). The distribution of the GSTO1 genotype was nearly equal between the control group and asthmatics, however, the distribution of the GSTO2 gene differed significantly between asthmatics and controls (Chi-squared test). Subjects who had the GSTO2 homozygous D142 genotype were found to have an increased risk of asthma (OR 5.91; 95% CI 1.80-19.42). 4. The results show a potential association between the GST genes and asthma. This is particularly significant given that, in the literature, there are no epidemiological studies on alpha and omega classes of glutathione transferases in asthma. © 2010 Blackwell Publishing Asia Pty Ltd.Ltd. Source


Polimanti R.,University of Rome Tor Vergata | Polimanti R.,Clinical Physiopathology Center | Piacentini S.,University of Rome Tor Vergata | Lazzarin N.,Clinical Physiopathology Center | And 3 more authors.
Molecular and Cellular Biochemistry | Year: 2011

Involvement of genetic polymorphisms in arterial hypertension has already been reported, including GST genes, with contrasting results. The present research evaluates the possible association between GST gene polymorphisms and essential hypertension (EH) in an Italian population sample. 193 hypertensive subjects and 210 healthy controls were recruited. Buccal cells were collected from each subject using an oral swab and DNA was extracted using the phenol:chloroform:isoamilic alcohol method. GST SNPs were determined using the PCR-RFLP method, while GST null polymorphisms were determined using a Multiplex PCR. Among GST polymorphisms, only the frequency of the GSTT1 null phenotype was significantly higher in hypertensive patients than in normotensive participants. GSTT1 null individuals were significantly associated with increased risk of hypertension [P < 0.001; adjusted OR 2.24 (1.43-3.50)]. In sex-based analysis, the risk was significantly higher in female hypertensives [P < 0.001; adjusted OR 3.25 (1.78-5.95)] but not in male subjects. This study analyzed all GST gene that, in other research, have been studied in relation to arterial hypertension and the GSTO polymorphisms, showing an association only with GSTT1. The results for the GSTO genes represent the first analysis of this GST class in relation to blood pressure regulation. The association between the GSTT1 null phenotype and EH was confirmed in the overall population and in women, but not in men. These data suggest that GSTT1 could be a sex-specific candidate gene for EH. © Springer Science+Business Media, LLC. 2011. Source

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