Multiple Chemical Sensitivity – Current understanding of DNA

In this post, I want to list potential DNA polymorphism (SNPs) associated with MCS and then look at what we know about these polymorphisms.

” There is a significant overlap of MCS, CFS and fibromyalgie.”

Multiple chemical sensitivity syndrome (MCS)–suggestions for an extension of the U.S. MCS-case definition. 2005

Statistically significant differences between patient cases and controls were found with respect to rs1801133 (MTHFR), rs174546 (FADS1) and rs1801282 (PPARγ) polymorphisms…. Specific genetic polymorphisms associated with the syndrome or its pathogenesis were not identified.

Multiple chemical sensitivity: Genotypic characterization, nutritional status and quality of life in 52 patients. [2017]

We observed that high chemical sensitive individuals diagnosed by using Japanese criteria as MCS patients were more significantly associated with SOD2 polymorphisms.

Evaluation of genetic polymorphisms in patients with multiple chemical sensitivity. 2013

demonstrating an increased risk for MCS in Caucasian females homozygous for the CYP2D6 isoform and for the association of CYP2D6 and phase II NAT-2 polymorphisms [98]. Proneness to MCS was connected with NAT-2 polymorphism and homozygous deletions of M1 and T1 GST genes [99].

The Search for Reliable Biomarkers of Disease in Multiple Chemical Sensitivity and Other Environmental Intolerances 2011

A genetic predisposition for MCS may involve altered biotransformation of environmental chemicals. The CYP2D6 enzyme activates and inactivates toxins; the NAT2 enzyme bioactivates arylamines to protein-binding metabolites. A gene-gene interaction between CYP2D6 and NAT2 suggested that rapid metabolism for both enzymes may confer substantially elevated risk (OR = 18.7, P = 0.002)

Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR. 2004

No significant differences of the allelic distribution of geneticpolymorphisms in the genes for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were found between cases and controls. The results are in contrast to the study of McKeown-Eyssen and coworkers (2004) but in accordance with the German MCS multicenter study. 

Sequence variations in subjects with self-reported multiple chemical sensitivity (sMCS): a case-control study. 2008

No significant differences in the allelic distribution of genetic polymorphisms in the GSTM1, GSTT1, ALDH2 or PON1 genes were found among the four levels of each subscale, or between cases and controls.

Factors in genetic susceptibility in a chemical sensitive population using QEESI. 2012


  • Clean evidence for
    • MTHFR,
    • FADS1
    • PPARγ
    • CYP2D6
  • Disagreement for
    • SOD2
    • NAT-2
    • 5HTT,
    • NAT1,
    • PON1,
    • PON2



The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Methylenetetrahydrofolate reductase is important for a chemical reaction involving forms of the vitamin folate (also called vitamin B9). Specifically, this enzyme converts a molecule called 5,10-methylenetetrahydrofolate to a molecule called 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.

People with this condition often develop eye problems, abnormal blood clotting, skeletal abnormalities, and cognitive problems

US National Library of Medicine


” These results position Fads1 as an underappreciated regulator of inflammation initiation and resolution, and suggest that endogenously synthesized arachidonic acid and eicosapentaenoic acid are key determinates of inflammatory disease progression and liver X receptor signaling. ”

Δ-5 Fatty Acid Desaturase FADS1 Impacts Metabolic Disease by Balancing Proinflammatory and Proresolving Lipid Mediators

Single nucleotide polymorphisms (SNPs) of FADS1 and FADS2 may affect long-chain polyunsaturatedfatty acids (LC-PUFA) metabolism and have a potential role in the development of atopic (Allergic) diseases.[7] – Wikipedia


Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily of ligand-inducible transcription factors that regulate adipogenesis, lipid metabolism, cell proliferation, inflammation and insulin sensitization. 


PPAR-gamma decreases the inflammatory response of many cardiovascular cells, particularly endothelial cells.[30] PPAR-gamma activates the PON1 gene, increasing synthesis and release of paraoxonase 1 from the liver, reducing atherosclerosis.[31]

Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes activate PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. 


This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 25% of commonly prescribed drugs. Its substrates include antidepressants, antipsychotics, analgesics and antitussives, beta adrenergic blocking agents, antiarrythmics and antiemetics. The gene is highly polymorphic in the human population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme’s substrates. Some individuals with the poor metabolizer phenotype have no functional protein since they carry 2 null alleles whereas in other individuals the gene is absent. This gene can vary in copy number and individuals with the ultrarapid metabolizer phenotype can have 3 or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

US National Library of Medicine

Bottom Line

Using the above information, there seem to be some avenues that should be explore for MCS patients for researchers:

Scanning some MCS discussion groups, at least two of the above avenues appears to help some.

Treatment Status

A search on PubMed shows that modern medical science is still struggling on diagnosis of this condition.

There are many random attempts to treat (usually by people with magic bullets that they are trying to find things to treat):

A randomised, placebo-controlled trial of transcranial pulsed electromagnetic fields in patients with multiple chemical sensitivity. [2017] “PEMF treatment of 6 weeks showed no effect on functional impairments in MCS. ” sometimes with word-smithing to indicate some form of positive effect (which could also be a placebo effect). Two classic phrases:

  • “Significant improvement” – something appears better, but the evidence did not reach statistical significance.
  • “Statistical significant improvement” – maths said something improved, but not remission and may be a very small improvement.