The Association and Linkage of the HLA-A2 Class I Allele with Autism
Abstract
Previous research has revealed associations between autism and immune genes located in the human leukocyte antigen (HLA). To better understand which HLA genetic loci may be associated with autism, we compared the class I HLA-A and -B alleles in autistic probands with case control subjects from Caucasian families. The frequency of HLA-A2 alleles was significantly increased in autistic subjects compared with normal allelic frequencies from the National Marrow Donors Program (NMDP) (p = 0.0043 after allelic correction). The transmission disequilibrium test for the A2 allele revealed an increased frequency of inheritance for autistic children (p = 0.033). There were no significant associations of autism with HLA-B alleles; however, the A2-B44 and A2-B51 haplotypes were two times more frequent in autistic subjects. The association and linkage of the class I HLA-A2 allele with autism suggests its involvement in the etiology of autism. Possible roles are discussed for the HLA-A2 association in the presentation of microbial antigen within the central nervous system and/or in the establishment of synaptic and neuronal circuits in the developing brain.
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Class I A*01, A*02, and B*07 are positively associated with autism, while DRB1*03 and some DQB1 alleles are negatively associated.
“Other positively associated alleles are the class I A*01, A*02, and B*07, while DRB1*03 and some DQB1 alleles have been negatively associated with rates of autism (Al-Hakbany et al, 2014;Mostafa et al, 2013;Torres et al, 2006).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Torres et al, 2006
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- Authors
- Torres, A. R., Sweeten, T. L., Cutler, A., Bedke, B. J., Fillmore, M., Stubbs, E. G., & Odell, D.
- Affiliations
- Utah State University (US)
- Oregon Health & Science University (US)
- Corresponding author
- Torres, Anthony R.
- Venue
- Human Immunology
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 67
- Issue
- 4-5
- Pages
- 346-351
- ISSN
- 0198-8859 (ISSN-L)
- OpenAlex
- W2051686506
- Cited by
- 104
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 8 · 2014: 5 · 2013: 4 · 2012: 14
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Utah
- National Institutes of Health (5r03ns051549-02)
- National Institute of Neurological Disorders and Stroke (1R03NS51549)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- autism spectrum disorder, HLA-A2, HLA class I alleles, HLA-B alleles, HLA haplotypes, genetic association, genetic linkage, transmission disequilibrium test, immune-related genes, autism etiology
- MeSH terms
- Alleles, Autistic Disorder, Humans, Genetic Linkage, Histocompatibility Antigens Class I, HLA-A2 Antigen
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