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Mediators of Inflammation
Volume 2015, Article ID 245308, 10 pages
Research Article

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

1Centre of Innovative Biotechnological Investigations (Cibi-Nanolab), 197 Vernadskogo Prospekt, Moscow 119571, Russia
2Active Longevity Clinic “Institut Krasoty na Arbate”, 8 Maly Nikolopeskovsky lane, Moscow 119002, Russia
3Department of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, 98125 Messina, Italy
42nd Dermatology Division, Dermatology Institute (IDI IRCCS), Via dei Monti di Creta 104, 00167 Rome, Italy

Received 24 December 2014; Accepted 8 March 2015

Academic Editor: Oreste Gualillo

Copyright © 2015 Chiara De Luca et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.