title: Genetic susceptibility factors for multiple chemical sensitivity revisited.
abstract: Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with MCS, but findings are inconsistent. The purpose of this study was to investigate genetic susceptibility factors for MCS and self-reported chemical sensitivity in a population sample. Ninety six MCS patients and 1,207 controls from a general population divided into four severity groups of chemical sensitivity were genotyped for variants in the genes encoding cytochrome P450 2D6, arylamine N-acetyltransferase 2, paraoxonase 1, methylene tetrahydrofolate reductase, and the cholecystokinin 2 receptor. No hypotheses were consistently confirmed. An apparent association between number of active cytochrome P450 2D6 alleles and MCS status was not statistically significant (OR=1.2, p=0.28). Fast arylamine N-acetyltransferase 2 metaboliser status was associated with severity of chemical sensitivity only in the most severely affected group in the population sample (OR=3.1, p=0.04). The cholecystokinin 2 receptor allele with 21 CT repeats was associated with MCS when compared in post hoc analyses with all individuals from the population sample (p=0.02). Genetic variants in paraoxonase 1 and methylene tetrahydrofolate reductase were not associated with MSC or with self-reported chemical sensitivity in the population sample. Our results suggest that variants in the genes examined are of less importance to MCS than previously reported or that gene-environment interactions or significant degrees of genetic heterogeneity in MCS underlie inconsistent findings in the literature.
authors.affiliation: The Danish Research Centre for Chemical Sensitivities, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Gentofte, Denmark. nber0016@glo.regionh.dk
authors.forename: Nikolaj Drimer
authors.initials: ND
authors.lastname: Berg
authors.forename: Henrik Berg
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.forename: Charlotte
authors.initials: C
authors.lastname: Brasch-Andersen
authors.forename: Mogens
authors.initials: M
authors.lastname: Fenger
authors.forename: Asger
authors.initials: A
authors.lastname: Dirksen
authors.forename: Søren
authors.initials: S
authors.lastname: Vesterhauge
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Jesper
authors.initials: J
authors.lastname: Elberling
mesh_terms: D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D018777:Multiple Chemical Sensitivity / Q000235:genetics*; D043887:Receptor, Cholecystokinin B / Q000235:genetics*; D055815:Young Adult
chemical_list: D043887:Receptor, Cholecystokinin B; D019389:Cytochrome P-450 CYP2D6; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human