Factors in genetic susceptibility in a chemical sensitive population using QEESI

Abstract

Objectives Inherited impairment of xenobiotic metabo-

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

“…If the lack of GSTM1 activity, which detoxifies the reactive metabolites of benzo[a]pyrene and other polycyclic aromatic hydrocarbons, is due to homozygous deletion of the gene [86,87], GSTT1 weakness has been found to negatively impact on the metabolism of various potential carcinogens such as monohalomethanes, which are widely used as methylating agents, pesticides, and solvents [86,87]. Furthermore, GST cytosolic activity in olfactory epithelium, the highest among extrahepatic tissues [39,86], is of particular interest in MCS, where the role of odorous triggers is important. In fact, acetaldehyde is one of the most important chemicals that induce sick house syndrome and MCS [88].…”

“…The Arg192 isoform hydrolyzes paraoxon rapidly, whereas the Gln192 isoform acts slowly [92]. PON1 genes were associated with Gulf War Syndrome whose complaints of olfactory dysfunction are extensively shared with those of MCS [39]. On the other hand, the overlapping symptoms among MCS spectrum disorders have been found to possibly share some common pathogenetic features such as increased nitric oxide/peroxynitrite levels [57] and its consequences on the olfactory pathways [93].…”

“…In this vision, many attempts-with different results-have been conducted in order to highlight the possible relationships between genetic polymorphisms and quality of life tests and to depict possible routes of pathophysiological models underpinning the development of MCS-related complaints. Among the vast literature regarding the gene polymorphisms involved in MCS, the overall approach is, at least, to define the individual genetic profiles of enzymes involved in body detoxification from xenobiotics such as phase I metabolism cytochrome P450 monoxygenases (CYP450), phase II metabolism glutathione-S-transferase (GST) and N-acetyl-transferase (NAT2), antioxidant defense, namely mitochondrial superoxide dismutase (SOD2), paraoxonase 1 and 2 (PON1, PON2), endothelial and inducible nitric oxide synthase (NOS2, NOS3) as well as folate cycle/methylation (MTHFR) [10,31,[39][40][41][42][43][44][45][46]. The hypothesis underlying the above cited investigations was the fact that the extreme individual sensitivity in MCS patients could be related to the inherited impairment in xenobiotics/endobiotics metabolism and to a vicious cycle [47] including peroxynitrite overproduction and lipid peroxidation, possibly not coped by the impairment in SOD, catalase, glutathione peroxidase, and NOS enzyme activities [48].…”

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.…”