Dietary factors and endocrine consequences of multiple chemical sensitivity / Factores dietéticos y consecuencias endocrinas de la sensibilidad química múltiple

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A Proposal for Clinical Biomarkers in Multiple Chemical Sensitivity.

Multiple chemical sensitivity (MCS) is increasingly widespread disease, characterized by non-specific and recurring symptoms from various organs associated with exposure to common chemicals, even if inhaled at low concentrations, usually harmless for normal people. MCS is not yet well recognized from common point of view and for this reason affected patients risk marginalization and their symptoms are often trivialized. It is actually a devastating chronic disease that affects not only the patients in the daily routine but partly conditions their survival. Despite more than 50 years of research, the action mechanisms of MCS is still undefined. In this study we examine the theories about the etiopathogenesis of multiple chemical sensitivity that include genetic susceptibility factors, immunological factors, neurological factors and psychiatric factors. Since no specific diagnostic markers are currently available for the MCS, the diagnosis can only be supposed on the basis symptomatic criteria and patient's medical history. However new biochemical markers and diagnostic imaging techniques have emerged, useful to postulate at least the clinical-diagnostic hypothesis of MCS and in this paper we discuss a list of biomarkers studied for the diagnosis of MCS, based on the available scientific literature. At last but not least, we propose four-levels MCS tests that could help the clinician in the diagnosis of the pathology both through the use of quantifiable serological parameters, both through diagnostic tools, genetic testing and through clinical observation of symptoms.

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity.

Systemic inflammation and immune activation are striking features of multiple chemical sensitivity (MCS). The rs2298383 SNP of ADORA2A gene, coding for adenosine receptor type 2A (A2AR), has been involved in aberrant immune activation. Here we aimed to assess the prevalence of this SNP in 279 MCS patients and 238 healthy subjects, and its influence on ADORA2A, IFNG and IL4 transcript amounts in peripheral blood mononuclear cells of randomly selected patients (n = 70) and controls (n = 66) having different ADORA2A genotypes. The ADORA2A rs2298383 TT mutated genotype, significantly more frequent in MCS patients than in controls, was associated with a three-fold increased risk for MCS (O.R. = 2.86; C.I. 95% 1.99-4.12, p < 0.0001), while the CT genotype, highly prevalent among controls, resulted to be protective (O.R. = 0.33; C.I. 95% 0.224-0.475, p < 0.0001). Notably, ADORA2A mRNA levels were significantly lower, while IFNG, but not IL4, mRNA levels were significantly higher in TT MCS patients compared with controls. A significant negative correlation was found between ADORA2A and both IFNG and IL4, while a significant positive correlation was found between IFNG and IL4. These findings suggest that A2AR defective signaling may play a relevant role in PBMC shift towards a pro-inflammatory phenotype in MCS patients.

Olfactory-Related Quality of Life in Multiple Chemical Sensitivity: A Genetic-Acquired Factors Model.

Genetic polymorphisms as well as environmental exposures to chemical compounds, iatrogenic, psychological, and physical trauma may play a pathophysiological role in multiple chemical sensitivity (MCS) olfactory complaints, given that xenobiotic metabolism is influenced by sequence variations in genes of metabolizing enzymes. Thus, the aim of the present study was to depict-by means of multiple regression analysis-how different genetic conditions, grouped according to their function as well as clinical background and environmental exposure may interfere with those olfactory complaints referred by MCS patients. Therefore, MCS patients after gene polymorphism sequencing, the olfactory-related quality of life score-calculated by means of the Questionnaire of Olfactory Disorder in forty-six MCS patients-have been found to significantly rely on the phase I and II enzymes score and exposure to previous compounds and surgical treatments. The present work-implementing for the first time a genetic-acquired factors model on a regression analysis-further reinforces those theories, positing MCS as a complex, multifactorial, disease in which the genetic risk related to phase I and II enzymes involved in xenobiotic detoxification, olfactory, and neurodegenerative diseases play a necessary, but probably not sufficient role, along the pathophysiological route of the disease.

Multiple chemical sensitivity: pursuit of a scientific consensus, need for a public health response. Commentary.

On the international scene, Multiple Chemical Sensitivity (MCS) is defined, by several experts, as a multisystem syndrome that develops following chronic exposures to low doses of common chemical contaminants. Its general characteristics are, however, the object of conflicting opinions and a source of debate and research aimed at the appropriate nosological and therapeutic frameworks. In the face of a potentially debilitating trend, both in the occupational and in the economical and social sphere, the scientific community has not so far found an agreement. This problem leads patients and their associations to periodically claim some requests. The syndrome is also taken into consideration at a political level, especially due to the close connection with the problems related to environmental pollution and to decision making in the field of control and prevention. For these reasons we believe that an appropriate widespread surveillance network for MCS should be set up in Italy, capable of intercepting possible cases, analyzing them at a multidisciplinary level, and following their evolution.

Sensibilidad química múltiple: caracterización genotípica, estado nutricional y calidad de vida de 52 pacientes / Multiple chemical sensitivity: Genotypic characterization, nutritional status and quality of life in 52 patients

Antecedentes y objetivos: La sensibilidad química múltiple (SQM) es un síndrome multisistémico y crónico, de etiología desconocida. El objetivo de este estudio fue describir el estado nutricional y la calidad de vida, así como identificar posibles polimorfismos asociados al síndrome o a su patogenia. Pacientes y métodos: Estudio epidemiológico, descriptivo y transversal en pacientes con diagnóstico de SQM. Se recogieron datos antropométricos, composición corporal, fuerza muscular y calidad de vida. La selección de single nucleotide polymorphisms (SNP, ‘polimorfismos de un solo nucleótido’) se centró en genes asociados previamente a la SQM y genes que participan en rutas de estrés oxidativo e inflamación. Resultados: Se incluyeron 52 pacientes (93,2% del sexo femenino), con una edad media de 50,9 (10,3) años. Respecto a su estado nutricional (IMC), un 48% estaba fuera de rangos de normalidad (17% desnutrición y 32% sobrepeso y obesidad). Un 30% presentó masa muscular por debajo de la referencia para la edad, un 84% una fuerza muscular inferior al percentil 10 y un 51,8% un porcentaje de masa grasa elevado. Respecto a la calidad de vida, las puntuaciones medias estuvieron por debajo de las de otras enfermedades en todas las subescalas evaluadas. Se observaron diferencias significativas en las frecuencias encontradas entre casos y controles para los SNP rs1801133 (MTHFR), rs174546 (FADS1) y rs1801282 (PPARγ). Conclusión: Un elevado porcentaje de pacientes presentó un estado nutricional anormal con masa y fuerza muscular disminuidas, lo que reduce la calidad de vida de estos pacientes, ya mermada por la sintomatología. No se identificaron polimorfismos genéticos específicos asociados al síndrome o a su patogenia (AU)

Background and objectives: Multiple chemical sensitivity (MCS) is a chronic, multisystem syndrome of unknown etiology. The aim of the present study was to describe the nutritional status and quality of life of patients suffering from MCS, as well as to identify potential polymorphisms associated with this illness. Patients and methods: A cross-sectional, descriptive study was performed on patients with a diagnosis of MCS. Data on anthropometric and body composition variables, hand muscle strength and quality of life were collected. The selection of single nucleotide polymorphisms (SNPs) was based on genes previously associated with MCS and genes involved in inflammatory and oxidative stress pathways. Results: A total of 52 patients (93.2% female), with a mean age of 50.9 (10.3) years were included in the study. Among them, based on their BMI, 48% had an inadequate nutritional status (17% were underweight and 32% were overweight or obese). Thirty percent of patients had a low muscle mass for their age, 84% had muscle strength below the tenth percentile, and 51.8% had a high fat mass percentage. Regarding quality of life, all median scores were lower than those of other illnesses assessed for every subscale assessed. Statistically significant differences between patient cases and controls were found with respect to rs1801133 (MTHFR), rs174546 (FADS1) and rs1801282 (PPARγ) polymorphisms. Conclusion: A high percentage of patients had a poor nutritional status, low muscle strength and decreased muscle mass. These facts exacerbate the already-lower quality of life of these patients. Specific genetic polymorphisms associated with the syndrome or its pathogenesis were not identified (AU)

Multiple chemical sensitivity: Genotypic characterization, nutritional status and quality of life in 52 patients. / Sensibilidad química múltiple: caracterización genotípica, estado nutricional y calidad de vida de 52 pacientes.

BACKGROUND AND OBJECTIVES: Multiple chemical sensitivity (MCS) is a chronic, multisystem syndrome of unknown etiology. The aim of the present study was to describe the nutritional status and quality of life of patients suffering from MCS, as well as to identify potential polymorphisms associated with this illness. PATIENTS AND METHODS: A cross-sectional, descriptive study was performed on patients with a diagnosis of MCS. Data on anthropometric and body composition variables, hand muscle strength and quality of life were collected. The selection of single nucleotide polymorphisms (SNPs) was based on genes previously associated with MCS and genes involved in inflammatory and oxidative stress pathways. RESULTS: A total of 52 patients (93.2% female), with a mean age of 50.9 (10.3) years were included in the study. Among them, based on their BMI, 48% had an inadequate nutritional status (17% were underweight and 32% were overweight or obese). Thirty percent of patients had a low muscle mass for their age, 84% had muscle strength below the tenth percentile, and 51.8% had a high fat mass percentage. Regarding quality of life, all median scores were lower than those of other illnesses assessed for every subscale assessed. Statistically significant differences between patient cases and controls were found with respect to rs1801133 (MTHFR), rs174546 (FADS1) and rs1801282 (PPARγ) polymorphisms. CONCLUSION: A high percentage of patients had a poor nutritional status, low muscle strength and decreased muscle mass. These facts exacerbate the already-lower quality of life of these patients. Specific genetic polymorphisms associated with the syndrome or its pathogenesis were not identified.

Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session.

OBJECTIVES: To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure. DESIGN: Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure. SETTINGS: Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper. PARTICIPANTS: 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls. OUTCOME MEASURES: 17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels. RESULTS: MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls. CONCLUSIONS: MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.

Assessment of glutathione peroxidase-1 polymorphisms, oxidative stress and DNA damage in sensitivity-related illnesses.

AIMS: Oxidative stress increase is a key event for development of sensitivity-related illnesses (SRIs). The aim of this work was to evaluate the influence of a genetic variant in the antioxidant enzyme glutathione peroxidase (GPx1) on oxidative stress development in SRIs. MAIN METHODS: GPx1 rs1800668 genotype, as well as glutathione, ubiquinone, and DNA damage were assessed in 34 SRI patients and 36 healthy subjects. KEY FINDINGS: Total glutathione, reduced/oxidized glutathione, and ubiquinone were significantly decreased in cases compared with controls, while DNA fragmentation was significantly increased in patients. However, these differences were not associated to GPx1 genetic background. SIGNIFICANCE: GPx1 rs1800668 polymorphism does not play a major role in SRI-related oxidative stress development.

Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances.

Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A -2.5 kb (CCTTT) n as well as Ser608Leu and NOS3 -786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 -786T>C polymorphisms. Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A -2.5 kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5 kb (CCTTT) n polymorphism may be useful for differential diagnosis of various IEI.

Genetic factors in susceptibility to contact sensitivity.

There are clear differences in individual susceptibility to the development of contact allergies; some individuals readily become allergic to many chemicals, and others remain clinically tolerant of everything that they come into contact with. A great number of molecules and pathways can contribute to the perturbation by xenobiotics and the subsequent possible immune response. It is necessary to consider susceptibility in two ways: as allergen-specific and as non-allergen-specific. It is likely that different receptor pathways and processes will be involved in the different forms of susceptibility. As investigations of the genetic control of such susceptibility have failed to identify major genetic control, it is likely that small contributions will be made by many components. Whereas genome-wide associations and transcriptome analyses may reveal genetic clues in the future, explanation of how/why the expression of multiple molecular components can be controlled in a coordinated fashion may follow from investigation of microRNAs. It is becoming clear that microRNAs can regulate the expression of multiple genes and even multiple components of biochemical pathways.

Evaluation of genetic polymorphisms in patients with multiple chemical sensitivity.

OBJECTIVE: Multiple chemical sensitivity (MCS) is a chronic medical condition characterized by symptoms that the affect an individual's response to low-level chemical exposure. In this study, we identified a chemical sensitive population (CSP) and investigated the effect of genetic polymorphisms on their risk of chemical sensitivity. METHODS: A quick environment exposure sensitivity (QEESI) questionnaire was used to survey 324 Japanese male workers whose DNA samples had been collected and stored. The following genes, which encode enzymes affecting the metabolic activation of a large number of xenobiotic compounds, were selected and analyzed in order to determine their influence on genetic predisposition to CSP: cytochrome P450 (CYP) 2E1, N-acetyl transferase (NAT) 2, glutathione S-transferase (GST) M1, GSTT1, GSTP1, low Km aldehyde dehydrogenase (ALDH2), and superoxide dismutase (SOD) 2. RESULTS: Significant case-control distributed differences were observed in SOD2 polymorphisms and allele frequency distribution in high chemical sensitive subjects. Both the significant adjusted OR of 4.30 (95% CI, 1.23-15.03) and 4.53 (95% CI, 1.52-13.51) were observed in SOD2 Ala/Ala and Val/Ala compared to Val/Val and in SOD2 Ala/Ala compared to Val/Ala compared to Val/Val genetic analysis in the high chemical sensitivity case-control study. CONCLUSIONS: We observed that high chemical sensitive individuals diagnosed by using Japanese criteria as MCS patients were more significantly associated with SOD2 polymorphisms.

Factors in genetic susceptibility in a chemical sensitive population using QEESI.

OBJECTIVES: Inherited impairment of xenobiotic metabolism is a postulated mechanism underlying environmentally associated pathogeneses such as multiple chemical sensitivity (MCS). Using the Quick Environmental Exposure and Sensitivity Inventory (QEESI), we defined people who have a strong response to chemical substances as "chemical sensitive populations (CSP)." The aim of this study is to evaluate the condition of subjects sensitive to chemicals and to analyze their genotypes in order to identify susceptibility factors in CSPs in Japanese populations. METHODS: A total of 1,084 employees of Japanese companies were surveyed using the QEESI, history of MCS, and sick house syndrome. The common genotypes of the participants were analyzed for glutathione S-transferase (GST) M1, GSTT1, aldehyde dehydrogenase2 (ALDH2), and paraoxonase1 (PON1) in order to identify factors in the susceptibility to sensitivity to chemicals. RESULTS: Four subjects had history of diagnosis of MCS; no subjects had diagnosis of sick house syndrome. The subjects were divided into four levels according to scores of 0, 1-19, 20-39, and 40 or more on three of the QEESI subscales. In addition, we used the MCS criteria by Hojo to differentiate between cases (CSP) and controls. No significant differences in the allelic distribution of genetic polymorphisms in the GSTM1, GSTT1, ALDH2 or PON1 genes were found among the four levels of each subscale, or between cases and controls. CONCLUSIONS: Our findings suggest that the common genotypes of GSTM1, GSTT1, ALDH2, and PON1 are of little importance to CSP in a Japanese population.

Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes.

BACKGROUND: Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I/phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined. OBJECTIVES: We sought for genetic, immunological, and metabolic markers in MCS. METHODS: We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy controls for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST, glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined. RESULTS: Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased. CONCLUSIONS: Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS.

Genetic susceptibility factors for multiple chemical sensitivity revisited.

Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with MCS, but findings are inconsistent. The purpose of this study was to investigate genetic susceptibility factors for MCS and self-reported chemical sensitivity in a population sample. Ninety six MCS patients and 1,207 controls from a general population divided into four severity groups of chemical sensitivity were genotyped for variants in the genes encoding cytochrome P450 2D6, arylamine N-acetyltransferase 2, paraoxonase 1, methylene tetrahydrofolate reductase, and the cholecystokinin 2 receptor. No hypotheses were consistently confirmed. An apparent association between number of active cytochrome P450 2D6 alleles and MCS status was not statistically significant (OR=1.2, p=0.28). Fast arylamine N-acetyltransferase 2 metaboliser status was associated with severity of chemical sensitivity only in the most severely affected group in the population sample (OR=3.1, p=0.04). The cholecystokinin 2 receptor allele with 21 CT repeats was associated with MCS when compared in post hoc analyses with all individuals from the population sample (p=0.02). Genetic variants in paraoxonase 1 and methylene tetrahydrofolate reductase were not associated with MSC or with self-reported chemical sensitivity in the population sample. Our results suggest that variants in the genes examined are of less importance to MCS than previously reported or that gene-environment interactions or significant degrees of genetic heterogeneity in MCS underlie inconsistent findings in the literature.

A twin study of perfume-related respiratory symptoms.

Respiratory symptoms from environmental perfume exposure are main complaints in patients with multiple chemical sensitivities and often coincide with asthma and or eczema. In this population-based twin study we estimate the heritability of respiratory symptoms related to perfume and if co-occurrences of the symptoms in asthma, atopic dermatitis, hand eczema or contact allergy are influenced by environmental or genetic factors common with these diseases. In total 4,128 twin individuals (82%) responded to a questionnaire. The heritability of respiratory symptoms related to perfume is 0.35, 95%CI 0.14-0.54. Significant associations (p<0.05) between perfume-related respiratory symptoms and asthma, atopic dermatitis, hand eczema or contact allergy are not attributable to shared genetic or shared environmental/familial factors, except possibly for atopic dermatitis where genetic pleiotropy with respiratory symptoms to perfume is suggested by an estimated genetic correlation of 0.39, 95%CI 0.09-0.72.

The chemical defensive system in the pathobiology of idiopathic environment-associated diseases.

Chemical defensive system consisting of bio-sensoring, transmitting, and responsive elements has been evolved to protect multi-cellular organisms against environmental chemical insults (xenobiotics) and to maintain homeostasis of endogenous low molecular weight metabolites (endobiotics). Both genetic and epigenetic defects of the system in association with carcinogenesis and individual sensitivity to anti-tumor therapies have been intensely studied. Recently, several non-tumor human pathologies with evident environmental components such as rather rare functional syndromes (multiple chemical sensitivity, chronic fatigue, Persian Gulf, and fibromyalgia now collectively labeled as idiopathic environmental intolerances) and common diseases (vitiligo and systemic lupus erythematosus) have become subjects of the research on the impaired metabolism and detoxification of xenobiotics and endogenous toxins. Here, we collected and critically reviewed epidemiological, genetic, and biochemical data on the involvement and possible role of cytochrome P450 super family enzymes, glutathione-S-transferase isozymes, catechol-O-methyl-transferase, UDP-glucuronosyl transferases, and proteins detoxifying inorganic and organic peroxides (catalase, glutathione peroxidase, and peroxiredoxin) in the above pathologies. Genetic predisposition assessed mainly by single nucleotide polymorphism and gene expression analyses revealed correlations between defects in genes encoding xenobiotic-metabolizing and/or detoxifying enzymes and risk/severity of these syndromes/diseases. Proteome analysis identified abnormal expression of the enzymes. Their functions were affected epigenetically leading to metabolic impairment and, as a consequence, to the negative health outcomes shared by some of these pathologies. Data obtained so far suggest that distinct components of the chemical defensive system could be suitable molecular targets for future pathogenic therapies.

Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control.

New studies have revealed an essential role for TRPA1, a sensory neuronal TRP ion channel, in airway chemosensation and inflammation. TRPA1 is activated by chlorine, reactive oxygen species, and noxious constituents of smoke and smog, initiating irritation and airway reflex responses. Together with TRPV1, the capsaicin receptor, TRPA1 may contribute to chemical hypersensitivity, chronic cough, and airway inflammation in asthma, COPD, and reactive airway dysfunction syndrome.

Sequence variations in subjects with self-reported multiple chemical sensitivity (sMCS): a case-control study.

Polymorphisms in several genes contribute to interindividual differences in the metabolism of xenobiotics, and may lead to toxicity and disease. The balance between activation and/or detoxification processes may influence an individual's susceptibility to disease. One postulated mechanism underlying multiple chemical sensitivity (MCS) is based on increased metabolism of xenobiotics. The aim of the present study was to determine such polymorphisms in cases with self-reported MCS (sMCS) and controls. sMCS cases (14 men, 45 women, mean age: 48 yr) and controls (14 men, 26 women, mean age: 44 yr) of the same anthroposphere were characterized using the MCS-questionnaire from Huppe and coworkers (2000) and a standardized questionnaire for living conditions and living factors. Allelic frequencies of genomic variations for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were determined. The MCS questionnaire from Huppe et al. (2000) differentiated between cases and controls with 87.5% sensitivity and 90% specificity. Compared to controls the sMCS cases had lower exposures, especially to odorous factors, and worse social conditions. No significant differences of the allelic distribution of genetic polymorphisms in the genes for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were found between cases and controls. The results are in contrast to the study of McKeown-Eyssen and coworkers (2004) but in accordance with the German MCS multicenter study. Although the MCS questionnaire from Huppe et al. (2000) allowed us to differentiate sMCS cases and controls, it was not strong enough for a discrimination based on sequence variations in genes for enzymes involved in xenobiotic metabolism. Therefore, further research needs to focus on a unique phenomenological characterization of MCS.