50 research outputs found
HapMap-based study of human soluble GSTs: the role of natural selection in shaping the SNP diversity of xenobiotic-metabolizing genes
No full textFunctional diversity of the glutathione peroxidase gene family among human populations: implications for genetic predisposition to disease and drug response
No full textAim: To analyze the human genetic variation of glutathione peroxidases (GPX), estimating the functional differences among human populations and suggesting interethnic differences in predisposition to disease and drug response. Materials & methods: Using 1000 Genomes Project data, we analyzed 723 GPX variants in 1092 individuals belonging to 14 populations. Combining functional prediction analyses of coding and noncoding variants, we developed a method to estimate haplotype functionality. Results: GPX rare variants have a higher functional impact than common variants. The frequency among Asian patients of haplotypes associated with normal functionality is significantly higher for GPX1 and lower for GPX3 than for non-Asian patients; no adaptation signals in GPX1 and GPX3 were found in Asian patients. Conclusion: GPX1 and GPX3 differences may be associated with alterations in antioxidant capacity and redox regulation, which suggests diverse susceptibility to complex disease and diverse response to relevant drugs in Asians compared with individuals with other ethnic origins
Glutathione S-transferase gene polymorphisms and air pollution as interactive risk factors for asthma in a multicentre Italian field study: A preliminary study
No full textBackground: Asthma is one of the most common chronic diseases. Several studies have indicated that
oxidative stress impairs pulmonary function. Glutathione S-transferases (GSTs) are believed to be
critical in the protection of cells from reactive oxygen species.
Aim: In this case-control study we analysed the possible association between polymorphism in several
cytosolic GST genes, air pollution and asthma development.
Methods: Genotyping of GSTM1 and GSTT1 genes was carried out by a multiplex PCR; GSTA1,
GSTO1, GSTO2, GSTP1 polymorphisms were determined using the PCR-RFLP method. Data on
atmospheric pollutants were collected by the regional air-quality monitoring network.
Results: Among all the polymorphisms studied, the frequencies of GSTA1, GSTM1, GSTO2 and
GSTT1 genotypes found in the group of asthmatic patients seem to differ from the frequencies of those
found in the control group. Air pollutants were analysed and the air quality parameters considered
proved to be significantly different, and therefore suitable for this study.
Conclusion: The final result of this research should hopefully lead to a better understanding of gene–
environment interactions, so allowing earlier prediction and diagnosis of asthma disease and providing
an efficient means of prevention
Blood polymorphism frequencies in the T ofinu, the "Water Men" of Southern Benin
No full textInformations on the genetic constitution (AcP, EsD, PGMl> AK, 6-PGD, Hb, Hp, Cp and Gc blood systems) of the Tofinu, a lacustrine population living in the pile-work of the Guinean coast (Southern Benin), are reported. The Tofinu gene fre¬quencies are much as would be expected from the geographical position of this country.
The AcP, Hp and Hb fJ gene frequencies are compared with those of the other eth¬nic groups of Southern Benin as the Goun, Fon, Djedje, and Nago, using the contingen¬cy chi-square test of homogeneity. On the average, the five groups do not show any sig¬nificant differences. Thus it results that there seems to be a common genetic origin and that the cultural-linguistic differentiation followed the evolutive biological process for the populations of this country
GSTO2*N142D gene polymorphism associated with hypothyroidism in Italian patients
No full textHypothyroidism is a multifactorial endocrinal disease characterized by abnormally low thyroid hormone production. Thyroiditis is one of the primary causes of hypothyroidism, as it is an increasing level of inflammation in the thyroid gland that could be due to a failure of the anti-inflammatory response. Glutathione S-transferases are biomarkers of inflammation and oxidative stress. These phase II enzymes play a relevant role in detoxifying xenobiotic compounds. Particular attention has been focused on GSTA1, GSTM1, GSTO2, GSTP1, and GSTT1 genes to evaluate if GST gene polymorphisms are associated with hypothyroidism. We screened a case-control population (patients with hypothyroidism n = 110, controls n = 122) to analyze GST gene polymorphisms. GST SNPs were determined using the PCR-RFLP method, while GST null polymorphisms were determined using a Multiplex PCR. In this study, we found differences in genotype distribution between hypothyroid individuals and controls only for the GSTO2*N142D polymorphism. Logistic regression analysis, after adjustment for age and sex, confirmed this positive association (OR = 4.56; 95 % CI 1.22-17.00; p = 0.009). The GSTO2 enzyme can catalyze several reactions important for countering oxidative stress: subjects with the D142 allele may have a deficiency in the antioxidant enzymatic system. A decrease in antioxidant capacity may trigger increased oxidative stress. Previous studies have highlighted the role of GST enzymes in inflammation disorders, but no data are available on their role in hypothyroidism. Our results suggest that GSTO2 could increase disease risk susceptibility and could act as a risk factor for hypothyroidism in Italian patients
Distribution of some erythrocyte enzyme polymorphisms in Emilia Romagna (Northern Italy).
No full textGlutathione S-transferase ω class (GSTO) polymorphisms in a sample from Rome (Central Italy).
No full textGlutathione S-transferases are a superfamily of enzymes that are involved in biotransformation of
drugs, xenobiotics and play a fundamental role in the protection of cells from oxidative stress. In
humans, the recently described GST Omega class contains two expressed genes GSTO1 and GSTO2,
located on chromosome 10 (10q24.3). Four polymorphisms in GSTO genes have been identified
in ethnic groups: GSTO1*A140D (rs4925), GSTO1*E155del (rs56204475), GSTO1*E208K
(rs11509438) and GSTO2*N142D (rs156697). This study provides the allele frequencies of
GSTO polymorphism in a sample consisting of 116 apparently healthy individuals of both sexes
from Rome (Central Italy). Detection of GSTO1*A140D and GSTO2*N142D alleles was performed
by PCR-RFLP analysis, while GSTO1*E155del and GSTO1*E208K alleles were detected using the
Confronting Two-Pair Primers analysis (PCR-CTPP) and allele specific PCR, respectively. The
GSTO allele frequencies found in the Italian sample were included in the variability range observed
in European populations. Comparison between the data presented in this study and data in previous
studies showed different patterns among European, Asian and African populations
Functional variation of the transthyretin gene among human populations and its correlation with amyloidosis phenotypes.
No full textHuman genetic variation of CYP450 superfamily: analysis of functional diversity in worldwide populations
No full textThe present study aimed to investigate the human genetic diversity of the CYP450 superfamily in order to identify functional interethnic differences and analyze the role of CYP450 enzymes in human adaptation
