Background: Self-reported Chemical Sensitivity (SCS) is characterized by adverse effects due to exposure to low levels of chemical substances. The clinical manifestations of SCS are similar to the allergy and a high percentage of individuals with both diseases have been found. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with SCS. Objectives: The purpose of this study was to investigate whether allergic individuals with chemical sensitivity differed from allergic patients without chemical sensitivity with regard to the distribution of genotype and phenotype of CYP2C9, CYP2C19 and CYP2D6 polymorphisms. Methods: A total of 180 patients were enrolled for this study. A questionnaire was employed to collect information on individual chemical sensitivity while the Skin prick test and the PATCH test was used to verify the presence of an allergic condition against inhalants or contact allergens, respectively. For the evaluation of the CYP2C9, CYP2C19 and CYP2D6 polymorphisms, we used a strategy based on the amplification of the entire gene coupled to direct genomic DNA sequencing analysis. Results: Overall a total of 15 different CYP2C9, CYP2C19 and CYP2D6 haplotypes were identified in our population. If the five CYP2C9 and the two CYP2C19 identified alleles correspond to the previously described ones, four of the eight CYP2D6 haplotypes, detected in the study group, present new SNPs combinations. These new suballeles were categorized as CYP2D6*2M Salento Variant 1, CYP2D6*35B Salento Variant 2, CYP2D6*41 Salento Variant 3 and CYP2D6*4P Salento Variant 4 due to the presence of the key SNPs 2850 C>T, 31G>A, 2988 G>A and 1846 G>A, respectively. When the allergic individuals are divided into two groups according to their SCS score, we observed that the distribution of the CYP2D6 phenotypes was significantly different between the two groups. Conclusions: Our idea is that the application of the questionnaire that we have adopted has enabled us to diagnose a degree of chemical sensitivity, that results as comorbid of the allergic disease and in which a condition of poor or intermediate metabolizes for the detrimental CYP2D6 alleles, could represent a discriminant between the chemical sensitivity and the health state.

Assessment of CYP2C9, CYP2C19, and CYP2D6 Polymorphisms in Allergic Patients with Chemical Sensitivity

D'Attis S.;Massari S.;Bozzetti M. P.
2019

Abstract

Background: Self-reported Chemical Sensitivity (SCS) is characterized by adverse effects due to exposure to low levels of chemical substances. The clinical manifestations of SCS are similar to the allergy and a high percentage of individuals with both diseases have been found. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with SCS. Objectives: The purpose of this study was to investigate whether allergic individuals with chemical sensitivity differed from allergic patients without chemical sensitivity with regard to the distribution of genotype and phenotype of CYP2C9, CYP2C19 and CYP2D6 polymorphisms. Methods: A total of 180 patients were enrolled for this study. A questionnaire was employed to collect information on individual chemical sensitivity while the Skin prick test and the PATCH test was used to verify the presence of an allergic condition against inhalants or contact allergens, respectively. For the evaluation of the CYP2C9, CYP2C19 and CYP2D6 polymorphisms, we used a strategy based on the amplification of the entire gene coupled to direct genomic DNA sequencing analysis. Results: Overall a total of 15 different CYP2C9, CYP2C19 and CYP2D6 haplotypes were identified in our population. If the five CYP2C9 and the two CYP2C19 identified alleles correspond to the previously described ones, four of the eight CYP2D6 haplotypes, detected in the study group, present new SNPs combinations. These new suballeles were categorized as CYP2D6*2M Salento Variant 1, CYP2D6*35B Salento Variant 2, CYP2D6*41 Salento Variant 3 and CYP2D6*4P Salento Variant 4 due to the presence of the key SNPs 2850 C>T, 31G>A, 2988 G>A and 1846 G>A, respectively. When the allergic individuals are divided into two groups according to their SCS score, we observed that the distribution of the CYP2D6 phenotypes was significantly different between the two groups. Conclusions: Our idea is that the application of the questionnaire that we have adopted has enabled us to diagnose a degree of chemical sensitivity, that results as comorbid of the allergic disease and in which a condition of poor or intermediate metabolizes for the detrimental CYP2D6 alleles, could represent a discriminant between the chemical sensitivity and the health state.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11587/431562
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