Xenobiotic Sensor- And Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population
Daniela Caccamo1, Eleonora Cesareo2, Serena Mariani2, Desanka Raskovic3, Riccardo Ientile1, Monica Currò1, Korkina Liudmila2, DeLuca Chiara2
1Dept. of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, Messina, Italy
2Laboratory of Tissue Engineering and Skin Pathophysiology, Dermatology Institute (IDI IRCCS), Rome, Italy
32nd Dermatology Division, Dermatology Institute (IDI IRCCS), Rome, Italy
Corresponding Author: Dr. Chiara De Luca,PhD, Laboratory of Tissue
Engineering and Skin Pathophysiology, Dermatology Institute (IDI
IRCCS), Via Monti di Creta 104, Rome 00167, Italy,
Tel. +39 06 9112193, fax +39 06 9112192, e.mail c.deluca@idi.it.
Abstract
In the environmental sensitivity-related illnesses (SRI) multiple chemical sensitivity (MCS), chronic fatigue syndrome (FCS), 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, different methodological approaches. Here, we compared the frequency of gene polymorphisms of selected cytochrome P450 (CYP) metabolizing enzymes, and for the first time of the xenobiotic sensor Aryl hydrocarbon receptor (AHR), in the three cohorts of 145 diagnosed MCS, 94 suspected MCS, 80 FM/FCS patients, vs. 113 healthy controls. Contrary to our previous results on 110 Italian MCS patients, we showed, after careful evaluation of MCS established diagnostic criteria, exclusion of FM and FCS co-morbidities, and with techniques reaching 100% specificity and sensitivity for heterozygous genotypes, significantly different polymorphism distributions in-between patients' groups, and vs. controls, concerning CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2D6*4, CYP2D6*41 allele and heterozygous genotype frequencies, also confirmed
by disease risk Odds Ratios. Results allowed us to propose 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.
1Dept. of Biomedical Sciences and Morpho-Functional Imaging, Polyclinic University of Messina, Messina, Italy
2Laboratory of Tissue Engineering and Skin Pathophysiology, Dermatology Institute (IDI IRCCS), Rome, Italy
32nd Dermatology Division, Dermatology Institute (IDI IRCCS), Rome, Italy
Corresponding Author: Dr. Chiara De Luca,PhD, Laboratory of Tissue
Engineering and Skin Pathophysiology, Dermatology Institute (IDI
IRCCS), Via Monti di Creta 104, Rome 00167, Italy,
Tel. +39 06 9112193, fax +39 06 9112192, e.mail c.deluca@idi.it.
Abstract
In the environmental sensitivity-related illnesses (SRI) multiple chemical sensitivity (MCS), chronic fatigue syndrome (FCS), 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, different methodological approaches. Here, we compared the frequency of gene polymorphisms of selected cytochrome P450 (CYP) metabolizing enzymes, and for the first time of the xenobiotic sensor Aryl hydrocarbon receptor (AHR), in the three cohorts of 145 diagnosed MCS, 94 suspected MCS, 80 FM/FCS patients, vs. 113 healthy controls. Contrary to our previous results on 110 Italian MCS patients, we showed, after careful evaluation of MCS established diagnostic criteria, exclusion of FM and FCS co-morbidities, and with techniques reaching 100% specificity and sensitivity for heterozygous genotypes, significantly different polymorphism distributions in-between patients' groups, and vs. controls, concerning CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2D6*4, CYP2D6*41 allele and heterozygous genotype frequencies, also confirmed
by disease risk Odds Ratios. Results allowed us to propose 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.
