Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session

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.

Keywords: Chemical exposure; Exposure chamber; Gene expression; Multiple Chemical Sensitivity; qPCR.

Figure 1

Overview of the exposure chamber procedure and sampling of blood. During the precondition, participants were seated in the exposure chamber with the door open. The door was thereafter closed, and the chamber session began at minute 0. During the first 10 min of testing, no odorant was delivered into the chamber, after which n-butanol was released into the chamber and reached a peak concentration after about 8 min. The concentration remained at this peak level (3.7 ppm) for the remaining part of the exposure session. Venous blood samples was collected within 30 min prior to the exposure session (TP1), within 15 min postexposure session (TP2) and again 4 hours after the exposure session was terminated (TP3). TP, time point.

Figure 2

Ratios of relative gene expression in unexposed MCS versus healthy controls. Data represent ratios of mean with 95% CIs between gene expression levels in leucocytes from MCS participants and healthy controls. Full form of genes abbreviations are provided in table 1. ADRB2, adrenergic β-2 receptor; ASAH1, N-acylsphingosine amidohydrolase (acid ceramidase) 1; CAT, catalase; COMT, catechol-O-methyltransferase; IL, interleukin; MCS, multiple chemical sensitivity; NFKB1, nuclear factor of κ light polypeptide gene enhancer in B cells 1; P2RX4, purinergic receptor P2X, ligand-gated ion channel, 4; P2RX5, purinergic receptor P2X, ligand-gated ion channel, 5; SGPL1, sphingosine-1-phosphate lyase 1; TNF, tumour necrosis factor; TRPA1, transient receptor potential cation channel, subfamily A, member 1; TRPV1, transient receptor potential cation channel, subfamily V, member 1; TRPV4, transient receptor potential cation channel, subfamily V, member 4.

Figure 3

n-Butanol exposure and relative gene expression levels. Data are shown as mean levels with SD of IL-1β, IL-6, IL-10, NFKB, TRPV1, TRPV4, COMT and ASAH1 quantified in buffy coat samples from the MCS participants and control. Data is presented at each of the three TPs of sampling: within 30 min prior to the exposure (TP1), within 15 min postexposure (TP2) and 4 hours after the exposure session had been terminated (TP3). ASAH1, N-acylsphingosine amidohydrolase (acid ceramidase) 1; COMT, catechol-O-methyltransferase; IL, interleukin; MCS, multiple chemical sensitivity; NFKB1, nuclear factor of κ light polypeptide gene enhancer in B cells 1; TP, time point; TRPV1, transient receptor potential cation channel, subfamily V, member 1; TRPV4, transient receptor potential cation channel, subfamily V, member 4.