Lack of association between autism and four heavy metal regulatory genes

Sarah E. Owens, Marshall L. Summar, Kelli K. Ryckman, Jonathan L. Haines, Sara Reiss, Samantha R. Summar, Michael Aschner

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Autism is a common neurodevelopmental disorder with genetic and environmental components. Though unproven, genetic susceptibility to high mercury (Hg) body burden has been suggested as an autism risk factor in a subset of children. We hypothesized that exposure to " safe" Hg levels could be implicated in the etiology of autism if genetic susceptibility altered Hg's metabolism or intracellular compartmentalization. Genetic sequences of four genes implicated in the transport and response to Hg were screened for variation and association with autism. LAT1 and DMT1 function in Hg transport, and Hg exposure induces MTF1 and MT1a. We identified and characterized 74 variants in MT1a, DMT1, LAT1 and MTF1. Polymorphisms identified through screening 48 unrelated individuals from the general and autistic populations were evaluated for differences in allele frequencies using Fisher's exact test. Three variants with suggestive p-values <0.1 and four variants with significant p-values <0.05 were followed-up with TaqMan genotyping in a larger cohort of 204 patients and 323 control samples. The pedigree disequilibrium test was used to examine linkage and association. Analysis failed to show association with autism for any variant evaluated in both the initial screening set and the expanded cohort, suggesting that variations in the ability of the four genes studied to process and transport Hg may not play a significant role in the etiology of autism.

Original languageEnglish (US)
Pages (from-to)769-775
Number of pages7
JournalNeuroToxicology
Volume32
Issue number6
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

Regulator Genes
Autistic Disorder
Heavy Metals
Screening
Genes
Set theory
Polymorphism
Mercury
Metabolism
Genetic Predisposition to Disease
Body Burden
Aptitude
Pedigree
Gene Frequency
Population

Keywords

  • Autism
  • DMT1
  • LAT1
  • Mercury
  • MT1a
  • MTF1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Owens, S. E., Summar, M. L., Ryckman, K. K., Haines, J. L., Reiss, S., Summar, S. R., & Aschner, M. (2011). Lack of association between autism and four heavy metal regulatory genes. NeuroToxicology, 32(6), 769-775. https://doi.org/10.1016/j.neuro.2011.07.003

Lack of association between autism and four heavy metal regulatory genes. / Owens, Sarah E.; Summar, Marshall L.; Ryckman, Kelli K.; Haines, Jonathan L.; Reiss, Sara; Summar, Samantha R.; Aschner, Michael.

In: NeuroToxicology, Vol. 32, No. 6, 12.2011, p. 769-775.

Research output: Contribution to journalArticle

Owens, SE, Summar, ML, Ryckman, KK, Haines, JL, Reiss, S, Summar, SR & Aschner, M 2011, 'Lack of association between autism and four heavy metal regulatory genes', NeuroToxicology, vol. 32, no. 6, pp. 769-775. https://doi.org/10.1016/j.neuro.2011.07.003
Owens SE, Summar ML, Ryckman KK, Haines JL, Reiss S, Summar SR et al. Lack of association between autism and four heavy metal regulatory genes. NeuroToxicology. 2011 Dec;32(6):769-775. https://doi.org/10.1016/j.neuro.2011.07.003
Owens, Sarah E. ; Summar, Marshall L. ; Ryckman, Kelli K. ; Haines, Jonathan L. ; Reiss, Sara ; Summar, Samantha R. ; Aschner, Michael. / Lack of association between autism and four heavy metal regulatory genes. In: NeuroToxicology. 2011 ; Vol. 32, No. 6. pp. 769-775.
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