Cargando…
Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population
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 res...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725911/ https://www.ncbi.nlm.nih.gov/pubmed/23936614 http://dx.doi.org/10.1155/2013/831969 |
_version_ | 1782278599273873408 |
---|---|
author | Caccamo, Daniela Cesareo, Eleonora Mariani, Serena Raskovic, Desanka Ientile, Riccardo Currò, Monica Korkina, Liudmila De Luca, Chiara |
author_facet | Caccamo, Daniela Cesareo, Eleonora Mariani, Serena Raskovic, Desanka Ientile, Riccardo Currò, Monica Korkina, Liudmila De Luca, Chiara |
author_sort | Caccamo, Daniela |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3725911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-37259112013-08-09 Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population Caccamo, Daniela Cesareo, Eleonora Mariani, Serena Raskovic, Desanka Ientile, Riccardo Currò, Monica Korkina, Liudmila De Luca, Chiara Oxid Med Cell Longev Research Article 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. Hindawi Publishing Corporation 2013 2013-07-07 /pmc/articles/PMC3725911/ /pubmed/23936614 http://dx.doi.org/10.1155/2013/831969 Text en Copyright © 2013 Daniela Caccamo et al. https://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Article Caccamo, Daniela Cesareo, Eleonora Mariani, Serena Raskovic, Desanka Ientile, Riccardo Currò, Monica Korkina, Liudmila De Luca, Chiara Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population |
title | Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population |
title_full | Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population |
title_fullStr | Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population |
title_full_unstemmed | Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population |
title_short | Xenobiotic Sensor- and Metabolism-Related Gene Variants in Environmental Sensitivity-Related Illnesses: A Survey on the Italian Population |
title_sort | xenobiotic sensor- and metabolism-related gene variants in environmental sensitivity-related illnesses: a survey on the italian population |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725911/ https://www.ncbi.nlm.nih.gov/pubmed/23936614 http://dx.doi.org/10.1155/2013/831969 |
work_keys_str_mv | AT caccamodaniela xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation AT cesareoeleonora xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation AT marianiserena xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation AT raskovicdesanka xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation AT ientilericcardo xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation AT curromonica xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation AT korkinaliudmila xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation AT delucachiara xenobioticsensorandmetabolismrelatedgenevariantsinenvironmentalsensitivityrelatedillnessesasurveyontheitalianpopulation |