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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 831969, 9 pages
http://dx.doi.org/10.1155/2013/831969
Research Article

Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population

1Department of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, 98125 Messina, Italy
2Laboratory of Tissue Engineering and Skin Pathophysiology, Dermatology Institute (IDI IRCCS), Via Monti di Creta 104, 00167 Rome, Italy
32nd Dermatology Division, Dermatology Institute (IDI IRCCS), 00167 Rome, Italy

Received 4 March 2013; Accepted 19 May 2013

Academic Editor: Giuseppe Valacchi

Copyright © 2013 Daniela Caccamo 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.

Abstract

In the environmental sensitivity-related illnesses (SRIs), multiple chemical sensitivity (MCS), chronic fatigue syndrome (FCS), and fibromyalgia (FM), the search for genetic polymorphisms of phase I/II xenobiotic-metabolizing enzymes as suitable diagnostic biomarkers produced so far inconclusive results, due to patient heterogeneity, geographic/ethnic differences in genetic backgrounds, and different methodological approaches. Here, we compared the frequency of gene polymorphisms of selected cytochrome P450 (CYP) metabolizing enzymes and, for the first time, the frequency of the xenobiotic sensor Aryl hydrocarbon receptor (AHR) in the three cohorts of 156 diagnosed MCS, 94 suspected MCS, and 80 FM/FCS patients versus 113 healthy controls. We found significantly higher frequency of polymorphisms CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2D6*4 and CYP2D6*41 in patients compared with controls. This confirms that these genetic variants represent a genetic risk factor for SRI. Moreover, the compound heterozygosity for CYP2C9*2 and *3 variants was useful to discriminate between either MCS or FM/CFS versus SMCS, while the PM *41/*41 genotype discriminated between MCS and either SMCS or FM/CFS. The compound heterozygosity for CYP2C9 *1/*3 and CYP2D6 *1/*4 differentiated MCS and SMCS cases from FM/CFS ones. Interestingly, despite the distribution of the AHR Arg554Lys variant did not result significantly different between SRI cases and controls, it resulted useful for the discrimination between MCS and SMCS cases when considered within haplotypes in combination with CYP2C19 *1/*2 and CYP2D6 *1/*4. Results allowed us to propose the genotyping for these specific CYP variants, together with the AHR Arg554Lys variant, as reliable, cost-effective genetic parameters to be included in the still undefined biomarkers' panel for laboratory diagnosis of the main types of environmental-borne SRI.