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Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session
  1. Thomas M Dantoft1,2,3,
  2. Sine Skovbjerg3,
  3. Linus Andersson4,5,
  4. Anna-Sara Claeson4,
  5. Kaare Engkilde6,
  6. Nina Lind4,7,
  7. Steven Nordin4,
  8. Lars I Hellgren2
  1. 1Danish Research Centre for Chemical Sensitivities, Copenhagen University Hospital, Gentofte, Denmark
  2. 2Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
  3. 3Research Centre for Prevention and Health, Copenhagen, Denmark
  4. 4Department of Psychology, Umeå University, Umeå, Sweden
  5. 5Department of Occupational and Public Health Sciences, University of Gävle, Umeå, Sweden
  6. 6Department of Dermato-Allergology, The National Allergy Research Center, Copenhagen University Hospital Gentofte, Denmark
  7. 7Department of Economics, Swedish University of Agricultural Sciences, Uppsala, Sweden
  1. Correspondence to Dr Thomas M Dantoft; thomas.meinertz.dantoft{at}regionh.dk

Abstract

Objectives To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.

The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure.

Design Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure.

Settings Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper.

Participants 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls.

Outcome measures 17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels.

Results MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls.

Conclusions MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.

  • Multiple Chemical Sensitivity
  • Gene expression
  • qPCR
  • Chemical exposure
  • Exposure chamber

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors TMD, SS, LA, A-SC, KE, SN and LIH designed the study and wrote the study protocol. TMD, SS, SN, LA and A-SC secured the necessary funding. LA, A-SC and NL managed the recruitment and screening of study participants and they also took care of all contact with the study participants. TMD, LA, A-SC and NL carryout the chemical exposure work and TMD were responsible for simultaneous sample collection and handling. TMD, LIH and KE were responsible for the laboratory and analytical work and undertook data and statistical analysis. Authors TMD and LIH, KE and SS interpreted the gene expression data. TMD, SS, LA and LIH managed the literature searches and wrote the first draft of the manuscript. All authors participated in writing the paper, reviewed it for important intellectual content and approved the final version.

  • Funding This study was supported by grants from the Swedish Council for Working Life and Social Research (2011-0396), the Danish Ministry of the Environment, and the Swedish Foundation for Humanities and Social Sciences (M14-0375:1).

  • Competing interests None declared.

  • Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and approved by the Ethics Committee at Umeå University (Dnr 2013-19-31). All participants were given written and oral information about the study. All participants were given 500 Swedish kronor (∼€50) for their participation.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Anonymised raw quantitative PCR data as well as any computed data can be obtained by contacting the first author, TMD by email: thomas.meinertz.dantoft@regionh.dk

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