title: NFE2L2 Gene Variants and Arsenic Susceptibility: A Lymphoblastoid Model.
abstract: Arsenic (As) exposure is a major risk for several types of cancer and metabolic diseases such as diabetes. The transcription factor nuclear factor erythroid 2-related factor (Nrf2) is a key mediator in the cellular defense against As-induced adverse effects. The -653G/A and -617C/A gene variants modulate expression levels of the Nrf2 coding gene (NFE2L2) and are postulated to be associated with several illnesses. In this study the functional effect of these polymorphisms was investigated in the cellular sensitivity to As-mediated effects. Using quantitative real-time polymerase chain reaction (qRT-PCR) the basal levels of NFE2L2 mRNA and the induced levels of NFE2L2 and its target gene NQO1 were measured in lymphoblastoid cells carrying different genotypes for -653G/A and -617C/A polymorphisms following As exposure. The effects of different NFE2L2 gene genotypes on cell proliferation were also explored after chronic metal exposure. A tendency toward reduction in basal levels of NFE2L2 mRNA was noted in the heterozygous (GA/CA) and risk homozygous (AA/AA) genotypes of both polymorphisms in immortalized lymphoblastoid cells. Although the expression of NFE2L2 and NQO1 after acute acute iAs exposure was not markedly influenced by -653G/A and -617C/A genotype, it was found that these single-nucleotide polymorphisms (SNPs) were correlated with a differential sensitivity to chronic exposure to the metalloid. Further studies are needed to completely understand the role of -653G/A and -617C/A SNPs in regulation of the NFE2L2 gene.
authors.affiliation: a Universidad Autónoma de la Ciudad de México, Posgrado en Ciencias Genómicas , Mexico City , Mexico.
authors.forename: Mirna E
authors.initials: ME
authors.lastname: Morales-Marin
authors.forename: Emilio J
authors.initials: EJ
authors.lastname: Cordova
authors.forename: Federico
authors.initials: F
authors.lastname: Centeno
authors.forename: Angélica
authors.initials: A
authors.lastname: Martínez-Hernández
authors.forename: Angélica
authors.initials: A
authors.lastname: Méndez-García
authors.forename: Bertha
authors.initials: B
authors.lastname: Molina
authors.forename: Sara
authors.initials: S
authors.lastname: Frías
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004785:Environmental Pollutants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D001151:Arsenic