title: Lack of association between nuclear factor erythroid-derived 2-like 2 promoter gene polymorphisms and oxidative stress biomarkers in amyotrophic lateral sclerosis patients.
abstract: Oxidative stress involvement has been strongly hypothesized among the possible pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The intracellular redox balance is finely modulated by numerous complex mechanisms critical for cellular functions, among which the nuclear factor erythroid-derived 2-like 2 (NFE2L2/Nrf2) pathways. We genotyped, in a cohort of ALS patients (n = 145) and healthy controls (n = 168), three SNPs in Nrf2 gene promoter: -653 A/G, -651 G/A, and -617 C/A and evaluated, in a subset (n = 73) of patients, advanced oxidation protein products (AOPP), iron-reducing ability of plasma (FRAP), and plasma thiols (-SH) as oxidative damage peripheral biomarkers. Nrf2 polymorphisms were not different among patients and controls. Increased levels of AOPP (P < 0.05) and decreased levels of FRAP (P < 0.001) have been observed in ALS patients compared with controls, but no difference in -SH values was found. Furthermore, no association was found between biochemical markers of redox balance and Nrf2 polymorphisms. These data confirm an altered redox balance in ALS and indicate that, while being abnormally modified compared to controls, the oxidative stress biomarkers assessed in this study are independent from the -653 A/G, -651 G/A, and -617 C/A Nrf2 SNPs in ALS patients.
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Annalisa
authors.identifier: 0000-0001-7825-0649
authors.initials: A
authors.lastname: LoGerfo
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Chico
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Borgia
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Lucia
authors.identifier: 0000-0002-7173-7435
authors.initials: L
authors.lastname: Petrozzi
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rocchi
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Amelio
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Carlesi
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Elena
authors.identifier: 0000-0003-0134-5062
authors.initials: E
authors.lastname: Caldarazzo Ienco
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000097:blood; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D062107:Advanced Oxidation Protein Products; D015415:Biomarkers; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human