Supplementary Material for: Assessment of CYP2C9, CYP2C19, and CYP2D6 Polymorphisms in Allergic Patients with Chemical Sensitivity

<b><i>Background:</i></b> 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. <b><i>Objectives:</i></b> 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 <i>CYP2C9</i>, <i>CYP2C19</i>, and <i>CYP2D6</i> polymorphisms. <b><i>Methods:</i></b> 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 were used to verify the presence of an allergic condition against inhalants or contact allergens, respectively. For the evaluation of the <i>CYP2C9</i>, <i>CYP2C19</i>, and <i>CYP2D6</i> polymorphisms, we used a strategy based on the amplification of the entire gene coupled to direct genomic DNA sequencing analysis. <b><i>Results:</i></b> Overall, a total of 15 different <i>CYP2C9</i>, <i>CYP2C19</i>, and <i>CYP2D6</i> haplotypes were identified in our population. If the 5 <i>CYP2C9</i> and the 2 <i>CYP2C19</i> identified alleles correspond to the previously described ones, 4 of the 8 <i>CYP2D6</i> haplotypes, detected in the study group, present new SNPs combinations. These new suballeles were categorized as <i>CYP2D6</i>*<i>2M</i> Sa­lento Variant 1, <i>CYP2D6</i>*<i>35B</i> Salento Variant 2, <i>CYP2D6</i>*<i>41</i> Salento Variant 3, and <i>CYP2D6</i>*<i>4P</i> Salento Variant 4 due to the presence of the key SNPs 2,850 C&gt;T, 31G&gt;A, 2,988 G&gt;A, and 1,846 G&gt;A, respectively. When the allergic individuals are divided into 2 groups according to their SCS score, we observed that the distribution of the<i> CYP2D6</i> phenotypes was significantly different between the 2 groups. <b><i>Conclusions:</i></b> Our idea is that the application of the questionnaire that we have adopted has enabled us to diagnose a degree of chemical sensitivity, which results as comorbid of the allergic disease and in which a condition of poor or intermediate metabolizes for the detrimental <i>CYP2D6</i> alleles, could represent a discriminant between the chemical sensitivity and the health state.