Journal article
Lack of association between autism and four heavy metal regulatory genes
Neurotoxicology (Park Forest South), Vol.32(6), pp.769-775
12/2011
DOI: 10.1016/j.neuro.2011.07.003
PMCID: PMC3206176
PMID: 21798283
Abstract
► Polymorphisms identified through screening 48 unrelated individuals from the general and autistic populations were evaluated for differences in allele frequencies. ► Overall, we identified and characterized 75 variants in MT1a, DMT1, LAT1 and MTF1. ► Despite the fact that the analysis failed to show association with autism for any variant, we believe that given the debate (and unfounded theories on the role of thimerosal in the etiology of autism and related disorders, such as autism spectrum disorder) the results presented herein are highly important and will dispel some of the myths on Hg and these disorders.
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.
Details
- Title: Subtitle
- Lack of association between autism and four heavy metal regulatory genes
- Creators
- Sarah E Owens - Department of Pediatric Toxicology, Vanderbilt University School of Medicine, Nashville, TN, USAMarshall L Summar - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USAKelli K Ryckman - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USAJonathan L Haines - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USASara Reiss - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USASamantha R Summar - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USAMichael Aschner - Department of Pediatric Toxicology, Vanderbilt University School of Medicine, Nashville, TN, USA
- Resource Type
- Journal article
- Publication Details
- Neurotoxicology (Park Forest South), Vol.32(6), pp.769-775
- DOI
- 10.1016/j.neuro.2011.07.003
- PMID
- 21798283
- PMCID
- PMC3206176
- NLM abbreviation
- Neurotoxicology
- ISSN
- 0161-813X
- eISSN
- 1872-9711
- Publisher
- Elsevier B.V
- Grant note
- name: NIH, award: T32 ES007028, T32 MH065782; DOI: 10.13039/100000066, name: NIEHS, award: R01 07331
- Language
- English
- Date published
- 12/2011
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology
- Record Identifier
- 9984214678802771
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