Influence of the SOD2 A16V gene polymorphism on alterations of redox markers and erythrocyte membrane fatty acid profiles in patients with multiple chemical sensitivity

Abstract

Chronically increased oxidative stress has been reported in patients with multiple chemical sensitivity (MCS). Recently, a single nucleotide polymorphism of the gene coding for mitochondrial superoxide dismutase (SOD2), namely the missense substitution A16V (C47>T) resulting in alteration of SOD2 enzyme activity, has been reported to be associated with MCS. However, the influence of SOD2 A16V genetic background on redox status of patients with MCS has not yet been investigated. Here, the results of a retrospective analysis aimed to evaluate the role of the SOD2 A16V polymorphism in the alterations of antioxidant defense markers as well as fatty acid (FA) composition of erythrocyte membranes in 67 patients with MCS matched with 55 healthy controls is reported. The mutated SOD2 V16 variant was observed more frequently in the MCS group compared with the control group, and this difference was statistically significant. The most common genotype in both groups was the heterozygous SOD2 AV16 variant, whereas the mutated SOD2 VV16 variant was more frequently observed in the MCS group, although the difference was not significant. The MCS cohort showed significantly depleted levels of plasma total antioxidant activity, ubiquinol, erythrocyte reduced glutathione and membrane polyunsaturated FA levels, coupled with significant increases in glutathione peroxidase activity, likely accounting for sustained detoxification from lipoperoxides. Notably, the highest levels of oxidative stress were found in patients with MCS bearing the genotype SOD2 AA16, whereas intermediate levels were found in patients bearing the heterozygous AV16 genotype. Healthy subjects bearing the SOD2 AA16 genotype also showed increased oxidative stress compared with carriers of other SOD2 genotypes. Despite the need for further confirmations in larger cohorts, due to MCS population genetic heterogeneity, these preliminary findings suggest that SOD2 defective activity makes certain patients with MCS more susceptible to developing oxidative stress following a chronic daily exposure to pro-oxidant insults.

Chemical Intolerance and Mast Cell Activation: A Suspicious Synchronicity

“…Targeted genetic association studies have focused on (a) inflammatory and oxidative stress pathways [23]; (b) genes coding for enzymes that metabolize xenobiotics (e.g., SOD, NAT) [24][25][26]; (c) genetic polymorphisms that involve xenobiotic detoxification processes such as phase I and II enzymes [27,28]; (d) cytochrome P450 isoenzymes involved in metabolizing drugs [29]; and (e) genes such as PON1/PON2 involved in the detoxification of organophosphate pesticides [26,30]. However, reports from other researchers have been inconsistent [23,31,32].…”