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

Alhakbany, Manan A.; Awadallah, Sitalbanat; Al-Ayadhi, Laila

doi:10.1155/2014/242048

Cited by 21 publications

(24 citation statements)

References 39 publications

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“…Multiple studies have suggested HLA-DR4 as another risk factor, appearing at increased rates in children with autism as well as their mothers (Johnson et al, 2009;Lee et al, 2006). 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). Interestingly, Guerini et al (2015) discovered a 14-basepair insertion in HLA-G that was found more often in individuals with ASD and their mothers.…”

Section: Immunogenetic Factorsmentioning

confidence: 99%

The Role of the Immune System in Autism Spectrum Disorder

Meltzer

Water

2016

Neuropsychopharmacol

384

293

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Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.

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Section: Immunogenetic Factorsmentioning

confidence: 99%

The Role of the Immune System in Autism Spectrum Disorder

Meltzer

Water

2016

Neuropsychopharmacol

384

293

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“…alleles were selected in another study, but none of these alleles showed consistent results (16). Al-Hakbany et al (28) could only find HLA-B * 07 significantly associated with ASD in his case-control study, the extended haplotype HLA-A * 02-B * 07 was significantly higher in ASD compared to controls. The reason that causes these conflicting results could be complex.…”

Section: Discussionmentioning

confidence: 91%

Association Between HLA-B Polymorphisms and Autism Spectrum Disorder in Chinese Population

Kang

Zhu

et al. 2020

Iran J Pediatr

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Objectives:The aim of this study was to investigate the association between 2 single-nucleotide polymorphisms (SNP) of HLA-B and autism spectrum disorder (ASD). Methods: We enrolled 84 ASD and 182 healthy children in case-control study, and 67 family trios in family-based study. Two tag SNPs (rs1058026, rs2770) in gene HLA-B were selected to determine the association with ASD. Chi-square test was used in case-control study, haplotype relative risk test (HRR) and transmission disequilibrium test (TDT) analysis were performed in family-based study. Results: SNP rs1058026 was found significantly associated with ASD in family-based study (P = 0.016 for HRR; P = 0.020 for TDT), but not in case-control study. Conversely, SNP rs2770 did not show association with ASD in both studies. Conclusions:The association observed from this study indicates that gene HLA-B might play a role in ASD in Chinese population.Informed Consent: Each subject or their guardians (for children) signed a written informed consent regarding the use of their samples and basic information when they were hospitalized.

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“…Similar to AD, other studies have also implicated the HLA-DRB5 region in PD risk [72]. In one small autism study, the class I allele B*07 and class II allele DQB1*06 : 02 were both associated with disease risk [73]. Finally, class II allele DQB1*06 : 02 has been associated with marked increased risk for [74,75], and worsened severity of [76,77], narcolepsy.…”

Section: Discussionmentioning

confidence: 92%

Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case–control study

et al. 2017

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BackgroundAlzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations.Methods and findingsBuilding on prior work linking the HLA to AD, we used a robust imputation method on two separate case–control cohorts to examine the relationship between HLA haplotypes and AD risk in 309 individuals (191 AD, 118 cognitively normal [CN] controls) from the San Francisco-based University of California, San Francisco (UCSF) Memory and Aging Center (collected between 1999–2015) and 11,381 individuals (5,728 AD, 5,653 CN controls) from the Alzheimer’s Disease Genetics Consortium (ADGC), a National Institute on Aging (NIA)-funded national data repository (reflecting samples collected between 1984–2012). We also examined cerebrospinal fluid (CSF) biomarker measures for patients seen between 2005–2007 and longitudinal cognitive data from the Alzheimer’s Disease Neuroimaging Initiative (n = 346, mean follow-up 3.15 ± 2.04 y in AD individuals) to assess the clinical relevance of identified risk haplotypes. The strongest association with AD risk occurred with major histocompatibility complex (MHC) haplotype A*03:01~B*07:02~DRB1*15:01~DQA1*01:02~DQB1*06:02 (p = 9.6 x 10−4, odds ratio [OR] [95% confidence interval] = 1.21 [1.08–1.37]) in the combined UCSF + ADGC cohort. Secondary analysis suggested that this effect may be driven primarily by individuals who are negative for the established AD genetic risk factor, apolipoprotein E (APOE) ɛ4. Separate analyses of class I and II haplotypes further supported the role of class I haplotype A*03:01~B*07:02 (p = 0.03, OR = 1.11 [1.01–1.23]) and class II haplotype DRB1*15:01- DQA1*01:02- DQB1*06:02 (DR15) (p = 0.03, OR = 1.08 [1.01–1.15]) as risk factors for AD. We followed up these findings in the clinical dataset representing the spectrum of cognitively normal controls, individuals with mild cognitive impairment, and individuals with AD to assess their relevance to disease. Carrying A*03:01~B*07:02 was associated with higher CSF amyloid levels (p = 0.03, β ± standard error = 47.19 ± 21.78). We also found a dose-dependent association between the DR15 haplotype and greater rates of cognitive decline (greater impairment on the 11-item Alzheimer’s Disease Assessment Scale cognitive subscale [ADAS11] over time [p = 0.03, β ± standard error = 0.7 ± 0.3]; worse forgetting score on the Rey Auditory Verbal Learning Test (RAVLT) over time [p = 0.02, β ± standard error = −0.2 ± 0.06]). In a subset of the same cohort, dose of DR15 was also asso...

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

Cited by 21 publications

References 39 publications

The Role of the Immune System in Autism Spectrum Disorder

The Role of the Immune System in Autism Spectrum Disorder

Association Between HLA-B Polymorphisms and Autism Spectrum Disorder in Chinese Population

Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case–control study

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