The Relationship of HLA Class I and II Alleles and Haplotypes with Autism: A Case Control Study

Manan Al-Hakbany,Sitalbanat Awadallah,Laila AL-Ayadhi

doi:10.1155/2014/242048

Manan Al-Hakbany, Sitalbanat Awadallah + Show 1 more

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https://doi.org/10.1155/2014/242048

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Journal: Autism research and treatment	Publication Date: Jan 1, 2014
Citations: 51	License type: CC BY 3.0

Affiliation: King Saud University

Abstract

Earlier reports showed the relationship between autism and immune genes located in the human leukocyte antigen (HLA). In this current study, we compared the HLA class I and class II alleles and haplotypes in 35 autistic children with 100 control subjects from Saudi Arabia, using PCR-SSP method and Luminex technology. In class I the HLA-A*01 (P = 0.03, OR 2.68), A*02 (P = 0.001, OR 3.02) and HLA-B*07 (P = 0.01, OR 3.27), were significantly associated with autism. Also, the haplotype A*02-B*07 was significantly higher in autistic patients than in controls (P = 0.007, OR 5.83). In class II, DRB1*1104 was significantly higher in patients than in controls (P = 0.001, OR 8.75). The DQB1*0202 (P = 0.001, OR 0.24), DQB1*0302 (P = 0.001, OR 0.14), and DQB1*0501 (P = 0.012, OR 0.25), were negatively associated with disease. While the four-loci genotype study showed that A*01-B*07-DRB1*0701-DQB1*0602 (P = 0.001, OR 41.9) and the A*31-B*51-DRB1*0103-DQB1*0302 (P = 0.012, OR 4.8) are positively associated with autism among Saudi patients. This is the first report on a foreseeable risk of association of HLA-B*07 allele with autism. Thus, HLA-B*07 allele and the closely linked haplotype A*01 B*07 DRB1*0701 DQB1*0602 may serve as a marker for genetic susceptibility to autism in Saudis.

Highlights

Autism spectrum disorders (ASD) are neurodevelopmental syndromes characterized by early childhood onset, associated with brain abnormalities [1]
ASD includes autistic disorder, Asperger’s syndrome, Rett syndrome, childhood disintegrative disorder (CDD), and pervasive developmental disorders not otherwise specified (PDD-NOS), as per the DSM-IV-TR classification according to American Psychatric Association, 2000
Many of the proteins encoded by the major histocompatibility complex (MHC) showed to be closely linked with the formation, refinement, maintenance, and plasticity of the brain [28, 29]

Summary

Introduction

Autism spectrum disorders (ASD) are neurodevelopmental syndromes characterized by early childhood onset, associated with brain abnormalities [1]. ASD includes autistic disorder, Asperger’s syndrome, Rett syndrome, childhood disintegrative disorder (CDD), and pervasive developmental disorders not otherwise specified (PDD-NOS), as per the DSM-IV-TR classification according to American Psychatric Association, 2000. The incidence of ASD has dramatically risen in the past two decades affecting 1 in 88 children (about 1 in 54 boys and 1 in 252 girls) in the United States [2]. Broader diagnostic criteria and increased medical knowledge have contributed to this perceived increase in disease incidence [3]. The aetiology of ASD is still unclear; both genetic and environmental causes are believed to contribute to the risk for the development of this disease spectrum. More evidence suggests that environmental factors, such as exposure to toxic compounds, teratogens, perinatal insults, and prenatal infections, may be responsible directly or indirectly for the immune mechanisms that mediate the nervous system impairments seen in ASD [4, 5]

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