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

Abstract

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.

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

“…Interestingly, given that A2AR is abundantly present in olfactory bulb [34], it is possible to hypothesize that a defective activation of A2AR signaling pathway, caused by genetic defects, may play a role in smell alterations that are reported by MCS patients. Indeed, it has recently been shown that olfactory complaints in MCS patients rely on a complex interaction between genetic and acquired factors, mainly represented by toxic environmental stimuli [35].…”

Food Implications in Central Sensitization Syndromes

“…Central sensitization induces many functional, molecular and structural modifications. As a consequence, the prospect of establishing a unique definition including all these disorders is remote [ 1 , 2 ]. Several neurobiological aspects have been postulated as the likely routes of pathological models, such as classical conditioning, biochemical disruptions and neurogenic inflammation [ 2 ].…”

“…As a consequence, the prospect of establishing a unique definition including all these disorders is remote [ 1 , 2 ]. Several neurobiological aspects have been postulated as the likely routes of pathological models, such as classical conditioning, biochemical disruptions and neurogenic inflammation [ 2 ]. These may play a role in a wide spectrum of physiopathological central nervous system responses associated with specific regions of the brain that are connected with emotional and motivational processing of information, like the limbic area (amygdala, hippocampus) and the olfactory and the auditory efferent systems [ 2 , 3 , 4 , 5 ].…”

“…Several neurobiological aspects have been postulated as the likely routes of pathological models, such as classical conditioning, biochemical disruptions and neurogenic inflammation [ 2 ]. These may play a role in a wide spectrum of physiopathological central nervous system responses associated with specific regions of the brain that are connected with emotional and motivational processing of information, like the limbic area (amygdala, hippocampus) and the olfactory and the auditory efferent systems [ 2 , 3 , 4 , 5 ]. This situation may explain the development of the physiopathological cascade underpinning CSS, such as autonomic, endocrine and immune disfunction, as well as multisensory perception disruption and some psychological abnormalities of conduct and temper in these patients (anxiety, depression, mood disorders) [ 3 , 4 ].…”

“…In addition, environmental factors and genetic components are involved in the development of CSS. In fact, several single nucleotide polymorphisms related to the presence of FM, CFS and MCS have been described [ 2 , 6 ]. Indeed, it has been hypothesized that specific genetic profiles of impairment in certain essential enzymes are involved in the optimal corporal endobiotic/xenobiotic detoxification (phase I and II), DNA methylation/repair pathways and antioxidant defense/oxidative stress, such as CYP450, GST, NAT2, MTHFR, SOD2, PON1, PON2, NOS2 and NOS3 genes [ 2 ].…”