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

Authors

  • Flora Tassone,

    Corresponding author
    1. Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California
    2. M.I.N.D. Institute, University of California Davis Medical Center, Davis, California
    • Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, One Shields Avenue, Davis, CA 95616
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  • Lihong Qi,

    1. M.I.N.D. Institute, University of California Davis Medical Center, Davis, California
    2. Rowe Program in Human Genetics, School of Medicine, University of California, Davis, California
    3. Department of Public Health Sciences, School of Medicine, University of California, Davis, California
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  • Wenting Zhang,

    1. Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California
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  • Robin L. Hansen,

    1. M.I.N.D. Institute, University of California Davis Medical Center, Davis, California
    2. Department of Pediatrics, School of Medicine, University of California, Davis, California
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  • Isaac N. Pessah,

    1. M.I.N.D. Institute, University of California Davis Medical Center, Davis, California
    2. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California
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  • Irva Hertz-Picciotto

    1. M.I.N.D. Institute, University of California Davis Medical Center, Davis, California
    2. Department of Public Health Sciences, School of Medicine, University of California, Davis, California
    3. UC Davis Center for Children's Environmental Health and Disease Prevention, University of California, Davis, California
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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. Autism Res2011,4:250–261. © 2011 International Society for Autism Research, Wiley Periodicals, Inc.

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