Association of HLA alleles with autism

Sayad, Arezou; Akbari, Mohammad Taghi; Noroozi, Rezvan; Omrani, Mir Davood; Inoko, Hidetoshi; Ghafouri‐Fard, Soudeh

doi:10.2147/ndt.s186673

Cited by 3 publications

(2 citation statements)

References 25 publications

(32 reference statements)

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“…Although HLA haplotypes might exert a pathogenic role in the neurodevelopmental process in ASD patients, particularly after microbial infection, any HLA haplotypes as markers of genetic susceptibility to ASD in the Iranian population could not be suggested. 30 A recent very large Genome-Wide Association Study (GWAS) failed to detect MHClinked signals in ASD. 31 These results may be due to the heterogeneity of the disease and/or the paucity of post-GWAS HLA imputation research in ASD.…”

Section: Discussionmentioning

confidence: 99%

HLA-DR4 gene expression in a sample of Egyptian autistic children and their mothers: is it a risk factor?

Elhossiny

El-Baz

AbdelAziz

et al. 2023

Egypt J Pediatr Allergy Immunol

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Background: Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder without a known cause. However, some autistic children experience immune malfunction and numerous studies noted that probands with autism and their mothers had higher HLA-DR4 frequencies than their fathers did. Probably, the mother's HLA-DR4 activity contributes to the phenotype of autism in her fetus. The purpose of this work was to investigate any potential link between the HLA-DR4 gene and autism. Methods: We conducted a controlled cross-sectional study on 100 subjects enrolled from the Children's Hospital of Ain Shams University. They comprised four groups: 25 autistic children, 25 mothers of the autistic children, 25 healthy children as a control group, and 25 mothers of the healthy children. All children underwent a detailed history taking, general and neurological examination, and IQ assessment using the Stanford Binet scale. Molecular HLA-DR typing was assessed in all subjects. The diagnosis of ASD was established using the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria. Severity was assessed using the childhood autism rating scale (CARS). Results: 45.5% of the autistic patients demonstrated the HLA DR4 allele compared to 36% of the control children. Up to 9.1% of cases of ASD had a double DR4 allele compared to 4% of the controls but with no significant statistical difference in-between. Also, 48 % of the autistic children's' mothers had the HLA DR4 allele compared to 24% of the control mothers but the difference did not reach a significant difference. On the other hand, the HLA DR3 haplotype was present in only 6.8 % of the patients' alleles compared to 24% of controls (p<0.05). Conclusion: The link of some HLA alleles to autism indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Wider scale studies are needed to validate our findings.

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Section: Discussionmentioning

confidence: 99%

HLA-DR4 gene expression in a sample of Egyptian autistic children and their mothers: is it a risk factor?

Elhossiny

El-Baz

AbdelAziz

et al. 2023

Egypt J Pediatr Allergy Immunol

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“…RORα is reduced in the cerebellum and PFC of post-mortem ASD brains (Hu et al, 2015), and the RORA gene is hypermethylated (and therefore less expressed) in lymphoblastoid cells of these patients (Nguyen et al, 2010). Additionally, not only are RORA genetic variants associated with ASD (Sayad et al, 2017), but treatment of adult BTBR mice (an ASD model) with a synthetic RORα agonist improved repetitive behaviors by upregulating RORα target genes that are down-regulated in ASD (Wang et al, 2016). But the role of RORα is not confined to ASD; its expression is altered in schizophrenia (Devanna and Vernes, 2014) and many of its single nucleotide polymorphisms are found in ADHD (Miller et al, 2013;Liu et al, 2021).…”

Section: Rorα and Neurodevelopmental Disordersmentioning

confidence: 99%

Cerebellum and neurodevelopmental disorders: RORα is a unifying force

Ribeiro¹,

Sherrard²

2023

Front. Cell. Neurosci.

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Errors of cerebellar development are increasingly acknowledged as risk factors for neuro-developmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and schizophrenia. Evidence has been assembled from cerebellar abnormalities in autistic patients, as well as a range of genetic mutations identified in human patients that affect the cerebellar circuit, particularly Purkinje cells, and are associated with deficits of motor function, learning and social behavior; traits that are commonly associated with autism and schizophrenia. However, NDDs, such as ASD and schizophrenia, also include systemic abnormalities, e.g., chronic inflammation, abnormal circadian rhythms etc., which cannot be explained by lesions that only affect the cerebellum. Here we bring together phenotypic, circuit and structural evidence supporting the contribution of cerebellar dysfunction in NDDs and propose that the transcription factor Retinoid-related Orphan Receptor alpha (RORα) provides the missing link underlying both cerebellar and systemic abnormalities observed in NDDs. We present the role of RORα in cerebellar development and how the abnormalities that occur due to RORα deficiency could explain NDD symptoms. We then focus on how RORα is linked to NDDs, particularly ASD and schizophrenia, and how its diverse extra-cerebral actions can explain the systemic components of these diseases. Finally, we discuss how RORα-deficiency is likely a driving force for NDDs through its induction of cerebellar developmental defects, which in turn affect downstream targets, and its regulation of extracerebral systems, such as inflammation, circadian rhythms, and sexual dimorphism.

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