Evaluation of Genetic Polymorphisms in Patients with Multiple Chemical Sensitivity

Abstract

ObjectiveMultiple 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.MethodsA 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.ResultsSignificant 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.ConclusionsWe observed that high chemical sensitive individuals diagnosed by using Japanese criteria as MCS patients were more significantly associated with SOD2 polymorphisms.

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

“…As a whole, these findings indicate that MCS patients have an impaired metabolism of xenobiotics, both in phase I and phase of body detoxification, and confirm previously reported observations [40,43,44,51,52].…”

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

“…Indeed, dramatically increased levels of reactive oxygen and nitrogen species (ROS, RNS), as well as pro-inflammatory cytokines and the presence of autoimmune antibodies, have been reported in MCS patients compared with healthy subjects [9][10][11][12][13][14]. Moreover, a link has been suggested between MCS and inherited or acquired defects in genes coding for enzymes involved in xenobiotic metabolism phase I and II, antioxidant defense, lipid metabolism and one-carbon pathway [11,12,[15][16][17][18][19][20][21]. The presence of polymorphic variants of xenobiotic-metabolizing enzymes, other than raising the risk of serious adverse reactions to drug treatment, can also increase the individual sensitivity to the environmental toxic burden, determining the development of chronic systemic oxidative stress and inflammation.…”

A case report of idiopathic environmental intolerance: A controversial and current issue

“…In this case, several genetic anomalies have favored an amplification of the sensitization to the xenobiotics to which the worker was exposed. Similar but not conclusive results were previously reported in studies that have investigated genotype in patients with IEI/MCS …”

“…Similar but not conclusive results were previously reported in studies that have investigated genotype in patients with IEI/MCS. 24,[48][49][50][51][52][53][54] Various mutations of antioxidant genes (GST, CAT, OGG1) and the slow CYP 2D6 phenotype have favored the maintenance of high blood and tissue levels of aromatic compounds, as evidenced by the notable presence of DNA-Hippuric acid adducts on the gene NAP2, and the triggering of inflammatory responses by inhalation or contact with such agents. With regard to the latter, high concentrations of such metabolite precursors such as benzalkonium or benzyl benzoate have been associated with death from acute asthma attack.…”