Arsenic exposure, genetic susceptibility and leukocyte telomere length in an Italian young adult population
| العنوان: | Arsenic exposure, genetic susceptibility and leukocyte telomere length in an Italian young adult population |
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| المؤلفون: | Maria Grazia Andreassi, Elisa Bustaffa, Antonella Mercuri, F. Faita, Fabrizio Bianchi, Andrea Borghini, Fabrizio Minichilli |
| المصدر: | Mutagenesis. 31:539-546 |
| بيانات النشر: | Oxford University Press (OUP), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, DNA Repair, DNA damage, Health, Toxicology and Mutagenesis, Population, chemistry.chemical_element, Biology, Toxicology, Polymorphism, Single Nucleotide, Arsenic, DNA Glycosylases, 03 medical and health sciences, XRCC1, Internal medicine, Genotype, Leukocytes, Genetics, medicine, Genetic predisposition, Humans, education, Genetics (clinical), Glutathione Transferase, education.field_of_study, DNA, Drug Tolerance, Environmental Exposure, Environmental exposure, Telomere, Molecular biology, DNA-Binding Proteins, X-ray Repair Cross Complementing Protein 1, 030104 developmental biology, Endocrinology, Italy, chemistry, Female, Gene-Environment Interaction, DNA Damage |
| الوصف: | Arsenic-induced health effects may be associated with critically shortened telomeres. However, few data are available on the effects of arsenic exposure on telomere length. The aim of this study was to investigate the effects of chronic arsenic exposure on leukocyte telomere length (LTL) as well as the contribution of common polymorphisms in genes implicated in arsenic metabolism (GSTT1 and GSTM1) and DNA repair (hOGG1 and XRCC1). A group of 241 healthy subjects was enrolled from four areas of Italy known to be affected by natural or anthropogenic arsenic pollution. Urine samples were tested for inorganic As (iAs), monomethylarsinic (MMA) and dimethylarsinic acid (DMA). LTL was evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Genotyping was carried out by PCR-RFLP on leukocyte DNA. In multiple linear regression analysis, LTL was significantly and inversely correlated with age (β = -0.231, P = 0.006) and showed a certain trend toward significance with iAs urinary concentration (log10 iAs, β = -0.106, P = 0.08). The genotype distribution showed significant associations between GSTT1 and the As concentration (log10 iAs, P = 0.01) and metabolite patterns (log10 DMA, P = 0.05) in the urine. However, GST genes did not interact with arsenic exposure in the modulation of LTL. Conversely, the combined presence of a higher level of iAs + MMA + DMA ≥ 19.3 μg/l (F = 6.0, P interaction = 0.01), Asi ≥ 3.86 (F = 3.9, P interaction = 0.04) μg/l, iAs + MMA + DMA ≥ 15 μg/l (F = 4.2, P interaction = 0.04) and hOGG1 Cys allele was associated with a significantly lower LTL. An interaction between XRCC1 Arg399Gln and arsenic exposure was also observed (all P interaction = 0.04). These findings suggest that telomere shortening may represent a mechanism that contributes to arsenic-related disease. The interaction of hOGG1 and XRCC1 DNA repair polymorphisms and exposure enhances telomeric DNA damage. Future studies are warranted to understand better the epidemiologic impact of arsenic on telomere function as well as to identify the subgroups of exposed subjects who need better health surveillance. |
| تدمد: | 1464-3804 0267-8357 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::232b747acf9d9c792185e15d785e5071Test https://doi.org/10.1093/mutage/gew017Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....232b747acf9d9c792185e15d785e5071 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14643804 02678357 |
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