title: Arsenic exposure, genetic susceptibility and leukocyte telomere length in an Italian young adult population.
abstract: 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.
authors.affiliation: Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Borghini
authors.affiliation: Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Faita
authors.affiliation: Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mercuri
authors.affiliation: Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Minichilli
authors.affiliation: Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bustaffa
authors.affiliation: Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bianchi
authors.affiliation: Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy andreassi@ifc.cnr.it.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D000328:Adult; D001151:Arsenic / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004361:Drug Tolerance / Q000235:genetics; D004781:Environmental Exposure; D005260:Female; D059647:Gene-Environment Interaction; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007558:Italy; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D001151:Arsenic; D004247:DNA; D045647:DNA Glycosylases; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C413545:glutathione S-transferase T1; C479058:oxoguanine glycosylase 1, human