Metabolic and Genetic Screening of Electromagnetic Hypersensitive Subjects as a Feasible Tool for Diagnostics and Intervention

Abstract

Growing numbers of “electromagnetic hypersensitive” (EHS) people worldwide self-report severely disabling, multiorgan, non-specific symptoms when exposed to low-dose electromagnetic radiations, often associated with symptoms of multiple chemical sensitivity (MCS) and/or other environmental “sensitivity-related illnesses” (SRI). This cluster of chronic inflammatory disorders still lacks validated pathogenetic mechanism, diagnostic biomarkers, and management guidelines. We hypothesized that SRI, not being merely psychogenic, may share organic determinants of impaired detoxification of common physic-chemical stressors. Based on our previous MCS studies, we tested a panel of 12 metabolic blood redox-related parameters and of selected drug-metabolizing-enzyme gene polymorphisms, on 153 EHS, 147 MCS, and 132 control Italians, confirming MCS altered (P < 0.05–0.0001) glutathione-(GSH), GSH-peroxidase/S-transferase, and catalase erythrocyte activities. We first described comparable—though milder—metabolic pro-oxidant/proinflammatory alterations in EHS with distinctively increased plasma coenzyme-Q10 oxidation ratio. Severe depletion of erythrocyte membrane polyunsaturated fatty acids with increased ω6/ω3 ratio was confirmed in MCS, but not in EHS. We also identified significantly (P = 0.003) altered distribution-versus-control of the CYP2C19∗1/∗2 SNP variants in EHS, and a 9.7-fold increased risk (OR: 95% C.I. = 1.3–74.5) of developing EHS for the haplotype (null)GSTT1 + (null)GSTM1 variants. Altogether, results on MCS and EHS strengthen our proposal to adopt this blood metabolic/genetic biomarkers' panel as suitable diagnostic tool for SRI.

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

“…In the last decade, literature data provided evidence for the association of MCS with increased oxidative/nitrosative stress and inflammation [9][10][11][12][13][14], likely resulting from defects in xenobiotic metabolism and antioxidant enzyme defenses [26]. A chronic imbalance in redox homeostasis promotes the development of inflammation mainly through the dysregulation of immune response cells and the activation of pro-inflammatory transcription factors [27].…”

“…To date the proposed etiopathogenetic mechanism involves an aberrant activation of the vicious cycle N-methyl-d-aspartate (NMDA)-nitric oxide/peroxynitrite triggered by various chemical agents, that ultimately lead to oxidative stress and activation of pro-inflammatory transcription factors [8]. 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].…”

“…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.…”

Long-term exposure to 835 MHz RF-EMF induces hyperactivity, autophagy and demyelination in the cortical neurons of mice

“…Thus, RF-EMF exposure could induce various neurological changes. Information of phenotypes or symptoms following EMF exposure is still lacking even though some of studies have been reported with respect to electromagnetic hypersensitivity following EMF exposure3233.…”

EUROPAEM EMF Guideline 2016 for the prevention, diagnosis and treatment of EMF-related health problems and illnesses

“…A study by De Luca et al, in 2014 on 153 EHS and 132 controls showed metabolic pro-oxidant/pro-inflammatory alterations in EHS like decreased erythrocyte glutathione S-transferase (GST) activity, decreased reduced glutathione (GSH) levels, increased erythrocyte glutathione peroxidase (GPX) activity, an increased ratio of oxidizedCoQ10/total-CoQ10 in plasma, and a 10-fold increased risk associated with EHS for the detoxifying enzymes glutathione S transferase haplotype (null) GSTT1+(null) GSTM1 variants (242).…”