Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances

Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflamm...

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Main Authors: Chiara De Luca, Agnese Gugliandolo, Carlo Calabrò, Monica Currò, Riccardo Ientile, Desanka Raskovic, Ludmila Korkina, Daniela Caccamo
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/245308
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author Chiara De Luca
Agnese Gugliandolo
Carlo Calabrò
Monica Currò
Riccardo Ientile
Desanka Raskovic
Ludmila Korkina
Daniela Caccamo
author_facet Chiara De Luca
Agnese Gugliandolo
Carlo Calabrò
Monica Currò
Riccardo Ientile
Desanka Raskovic
Ludmila Korkina
Daniela Caccamo
author_sort Chiara De Luca
collection DOAJ
description Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A −2.5 kb (CCTTT)n as well as Ser608Leu and NOS3 −786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 −786T>C polymorphisms. Interestingly, the NOS3 −786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A −2.5 kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 −786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A −2.5 kb (CCTTT)n polymorphism may be useful for differential diagnosis of various IEI.
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spelling doaj-art-069eff26342e4a16907c223de54bc2dd2025-08-20T02:03:42ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/245308245308Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental IntolerancesChiara De Luca0Agnese Gugliandolo1Carlo Calabrò2Monica Currò3Riccardo Ientile4Desanka Raskovic5Ludmila Korkina6Daniela Caccamo7Centre of Innovative Biotechnological Investigations (Cibi-Nanolab), 197 Vernadskogo Prospekt, Moscow 119571, RussiaDepartment of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, 98125 Messina, ItalyDepartment of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, 98125 Messina, ItalyDepartment of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, 98125 Messina, ItalyDepartment of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, 98125 Messina, Italy2nd Dermatology Division, Dermatology Institute (IDI IRCCS), Via dei Monti di Creta 104, 00167 Rome, ItalyCentre of Innovative Biotechnological Investigations (Cibi-Nanolab), 197 Vernadskogo Prospekt, Moscow 119571, RussiaDepartment of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, 98125 Messina, ItalyOxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A −2.5 kb (CCTTT)n as well as Ser608Leu and NOS3 −786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 −786T>C polymorphisms. Interestingly, the NOS3 −786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A −2.5 kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 −786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A −2.5 kb (CCTTT)n polymorphism may be useful for differential diagnosis of various IEI.http://dx.doi.org/10.1155/2015/245308
spellingShingle Chiara De Luca
Agnese Gugliandolo
Carlo Calabrò
Monica Currò
Riccardo Ientile
Desanka Raskovic
Ludmila Korkina
Daniela Caccamo
Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances
Mediators of Inflammation
title Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances
title_full Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances
title_fullStr Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances
title_full_unstemmed Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances
title_short Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances
title_sort role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances
url http://dx.doi.org/10.1155/2015/245308
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