A genome-wide SNP investigation of chemical intolerance

Abstract

Background: Chemical Intolerance (CI) also known as Multiple Chemical Sensitivity (MCS) is characterized by multi-system symptoms initiated by exposures to environmental toxins. Symptoms include fatigue, headache, mood changes, musculoskeletal pain, gastro-intestinal issues, and difficulties with memory/concentration. With mixed results, researchers have targeted specific genes to understand the genetic pathways associated with CI. This study is the first to apply a genome-wide, untargeted exploratory method. Methods: A high-density genotyping platform was used to perform a hypothesis-free search for genetic variants associated with CI in a set of 200 participants. Each CI patient was verified using a validated survey. The association between CI and single nucleotide polymorphisms (SNPs) was obtained using SOLAR (Sequential Oligogenic Linkage Analysis Routines). Gene-Chemical-Disease interactions were determined using the DisGeNET Database. Results: Several SNPs were identified which either increase or decrease the associated risk of CI. These SNPs include markers close to genes involved in mast cell activation pathways. Four chemicals were found to most alter the gene expressions of the identified SNPs (bisphenol A, valproic acid, aflatoxin B, and benzo(a)pyrene). There were common adverse health effects associated with the genes and the chemicals that influence them, Discussion: This study supports evidence of novel genetic components associated with CI that may interact with common ubiquitous chemical and drug exposures affecting gene expression. There is evidence of immunological function and mast cell activation. The identified health consequences of the genes and associated chemicals are common to individuals with CI and implies gene/chemical exposure interactions that may influence the development or exacerbation of symptoms associated with CI. However, conclusions drawn from this data should not underestimate the complexity of gene/environment. The identified chemicals affecting these genes are ubiquitous environmental exposures, entering the body through air, food, and water, suggesting the need for greater public health policy efforts in an effort to protect vulnerable individuals. Future studies of CI would benefit from a systems biology approach.

Keywords

• Chemical intolerance
• Genes
• Chemical exposure
• Health effects