MAOA, DBH, and SLC6A4 variants in CHARGE: A case-control study of autism spectrum disorders

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Abstract

Genetic factors are established to contribute to the development of autism. We examined three loci, serotonin transporter (SLC6A4), dopamine β-hydroxylase (DBH), and the variable number of tandem repeat promoter of the monoamine oxidase A (MAOA) for association with autism in participants from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, the first large-scale population-based case-control investigation of both environmental and genetic contributions to autism risk. Among male children enrolled in the CHARGE study we tested associations between each of the three polymorphisms and autism (AU) (n = 119), or a combined group of autism and other autism spectrum disorders (AU+ASD, which includes an additional n = 53) as compared with typically developing controls (TD, n = 137). The case-control association analysis showed neither SLC6A4 nor DBH to be statistically significantly associated with AU or ASD. However, the male children carrying 4 tandem repeats in the promoter region of the MAOA gene showed a two-fold higher risk of AU (or AU+ASD) than those carrying allele 3, adjusted for confounders (OR = 2.02, 95% CI = 1.12, 3.65, P = 0.02 for AU vs. TD, and OR = 2.05, 95% CI = 1.19, 3.53, P = 0.01 for ASD vs. TD). In addition, children of mothers homozygous for the 4 tandem repeat allele showed at least a three-fold higher risk of AU (or AU+ASD) than those with mothers homozygous for allele 3 (OR = 3.07, 95% CI = 1.19, 7.91, P = 0.02 for AU vs. TD, and OR = 3.26, 95% CI = 1.35, 7.89, P = 0.009 for AU+ASD vs. TD). These results suggest a potential role of the functional MAOA promoter alleles in the male child, the mother, or both in ASD.

Original languageEnglish (US)
Pages (from-to)250-261
Number of pages12
JournalAutism Research
Volume4
Issue number4
DOIs
StatePublished - Aug 2011

Fingerprint

Monoamine Oxidase
Autistic Disorder
Case-Control Studies
Alleles
Tandem Repeat Sequences
Autism Spectrum Disorder
Mothers
Serotonin Plasma Membrane Transport Proteins
Minisatellite Repeats
Mixed Function Oxygenases
Genetic Promoter Regions

Keywords

  • ASD
  • DBH
  • MAOA
  • Polymorphisms
  • SLC6A4

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)

Cite this

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title = "MAOA, DBH, and SLC6A4 variants in CHARGE: A case-control study of autism spectrum disorders",
abstract = "Genetic factors are established to contribute to the development of autism. We examined three loci, serotonin transporter (SLC6A4), dopamine β-hydroxylase (DBH), and the variable number of tandem repeat promoter of the monoamine oxidase A (MAOA) for association with autism in participants from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, the first large-scale population-based case-control investigation of both environmental and genetic contributions to autism risk. Among male children enrolled in the CHARGE study we tested associations between each of the three polymorphisms and autism (AU) (n = 119), or a combined group of autism and other autism spectrum disorders (AU+ASD, which includes an additional n = 53) as compared with typically developing controls (TD, n = 137). The case-control association analysis showed neither SLC6A4 nor DBH to be statistically significantly associated with AU or ASD. However, the male children carrying 4 tandem repeats in the promoter region of the MAOA gene showed a two-fold higher risk of AU (or AU+ASD) than those carrying allele 3, adjusted for confounders (OR = 2.02, 95{\%} CI = 1.12, 3.65, P = 0.02 for AU vs. TD, and OR = 2.05, 95{\%} CI = 1.19, 3.53, P = 0.01 for ASD vs. TD). In addition, children of mothers homozygous for the 4 tandem repeat allele showed at least a three-fold higher risk of AU (or AU+ASD) than those with mothers homozygous for allele 3 (OR = 3.07, 95{\%} CI = 1.19, 7.91, P = 0.02 for AU vs. TD, and OR = 3.26, 95{\%} CI = 1.35, 7.89, P = 0.009 for AU+ASD vs. TD). These results suggest a potential role of the functional MAOA promoter alleles in the male child, the mother, or both in ASD.",
keywords = "ASD, DBH, MAOA, Polymorphisms, SLC6A4",
author = "Flora Tassone and Lihong Qi and Wenting Zhang and Hansen, {Robin L} and Pessah, {Isaac N} and Irva Hertz-Picciotto",
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AB - Genetic factors are established to contribute to the development of autism. We examined three loci, serotonin transporter (SLC6A4), dopamine β-hydroxylase (DBH), and the variable number of tandem repeat promoter of the monoamine oxidase A (MAOA) for association with autism in participants from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, the first large-scale population-based case-control investigation of both environmental and genetic contributions to autism risk. Among male children enrolled in the CHARGE study we tested associations between each of the three polymorphisms and autism (AU) (n = 119), or a combined group of autism and other autism spectrum disorders (AU+ASD, which includes an additional n = 53) as compared with typically developing controls (TD, n = 137). The case-control association analysis showed neither SLC6A4 nor DBH to be statistically significantly associated with AU or ASD. However, the male children carrying 4 tandem repeats in the promoter region of the MAOA gene showed a two-fold higher risk of AU (or AU+ASD) than those carrying allele 3, adjusted for confounders (OR = 2.02, 95% CI = 1.12, 3.65, P = 0.02 for AU vs. TD, and OR = 2.05, 95% CI = 1.19, 3.53, P = 0.01 for ASD vs. TD). In addition, children of mothers homozygous for the 4 tandem repeat allele showed at least a three-fold higher risk of AU (or AU+ASD) than those with mothers homozygous for allele 3 (OR = 3.07, 95% CI = 1.19, 7.91, P = 0.02 for AU vs. TD, and OR = 3.26, 95% CI = 1.35, 7.89, P = 0.009 for AU+ASD vs. TD). These results suggest a potential role of the functional MAOA promoter alleles in the male child, the mother, or both in ASD.

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