Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB1*1501-DQB1*0602 haplotype

Miyagawa, Taku; Honda, Masashi; Kawashima, M.; Shimada, Mihoko; Tanaka, Susumu; Honda, Yoshiyuki; Tokunaga, Katsushi

doi:10.1038/jhg.2009.118

Cited by 24 publications

(22 citation statements)

References 12 publications

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“…Several previous studies reported the possibility that EHS is not homogeneous and HLA-DRB1*1501-DQB1*0602 haplotype-positive EHS is essentially different from haplotype-negative EHS (Honda et al 1998;Miyagawa et al 2009Miyagawa et al , 2010. Thus, EHS cases were subdivided into two groups, HLA-DRB1*1501-DQB1*0602 haplotype-positive and -negative EHS, for stratified analysis.…”

Section: Analysis Of Ehs Samplesmentioning

confidence: 98%

“…The significant association of SNP rs8119787 was observed again in HLA-positive EHS (P = 0.032; OR = 1.46; 95% CI = 0.98-2.17) ( Table 3). In addition, we focused on the idea that the previous studies suggested that HLA-positive EHS exhibits autoimmune pathogenesis, similar to narcolepsy (Honda et al 1998;Miyagawa et al 2010). NFATC2 is an immune-related gene and plays a role in the inducible expression of cytokine genes in T cells.…”

Section: Analysis Of Ehs Samplesmentioning

confidence: 99%

“…(2) absence of cataplexy; and (3) hypersomnia that cannot be explained by another sleep disorder, a medical or neurological disorder, a mental disorder, from medication use, or a substance abuse disorder (Honda et al 1986;Komada et al 2005;Miyagawa et al 2009Miyagawa et al , 2010. The diagnostic criteria for EHS correspond to narcolepsy without cataplexy and to most of the idiopathic hypersomnias without long sleep time, according to the International Classification of Sleep Disorders, second edition (ICSD-2).…”

Section: Subjectsmentioning

confidence: 99%

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An approach based on a genome-wide association study reveals candidate loci for narcolepsy

et al. 2010

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Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and a pathological manifestation of rapid eye movement during sleep. Narcoleptic pathogenesis is triggered by both genetic and environmental factors. Recently, development of genome-wide association studies (GWAS) has identified new genetic factors, with many more susceptibility genes yet to be elucidated. Using a new approach that consists of a combination of GWAS and an extensive database search for candidate genes, we picked up 202 candidate genes and performed a replication study in 222 narcoleptic patients and 380 controls. Statistical analysis indicated that six genes, NFATC2, SCP2, CACNA1C, TCRA, POLE, and FAM3D, were associated with narcolepsy (P<0.001). Some of these associations were further supported by gene expression analyses and an association study in essential hypersomnia (EHS), CNS hypersonia similar to narcolepsy. This novel approach will be applicable to other GWAS in the search of disease-related susceptibility genes.

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Section: Analysis Of Ehs Samplesmentioning

confidence: 98%

Section: Analysis Of Ehs Samplesmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

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An approach based on a genome-wide association study reveals candidate loci for narcolepsy

et al. 2010

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“…15 Recent genome-wide association studies of HLA-DQB1*0602-positive European Caucasians, healthy Americans, and narcoleptics with cataplexy have identified the existence of a polymorphism in the T-cell receptor alpha (TRA) gene. 16,17 The TRA gene encodes a protein that activates cytotoxic CD8 cells and CD4 helper cells, resulting in susceptibility to the destruction of hypocretinergic HLA-DQB1*0602-positive cells. 16,17 These results suggest that narcolepsy is an autoimmune disease with HLA haplotype and a TRA polymorphism as risk factors.…”

Section: Genetics Of Narcolepsymentioning

confidence: 99%

“…16,17 The TRA gene encodes a protein that activates cytotoxic CD8 cells and CD4 helper cells, resulting in susceptibility to the destruction of hypocretinergic HLA-DQB1*0602-positive cells. 16,17 These results suggest that narcolepsy is an autoimmune disease with HLA haplotype and a TRA polymorphism as risk factors.…”

Section: Genetics Of Narcolepsymentioning

confidence: 99%

Diretrizes brasileiras para o diagnóstico de narcolepsia

Alóe

Alves

Araújo

et al. 2010

Rev. Bras. Psiquiatr.

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Este artigo relata as conclusões da reunião de consenso com médicos especialistas sobre diagnóstico de narcolepsia baseada na revisão dos artigos sobre narcolepsia listados no Medline entre 1980 e 2010. A narcolepsia é uma doença crônica de início entre a primeira e segunda décadas de vida do indivíduo. Os sintomas essenciais são cataplexia e sonolência excessiva. A cataplexia é definida como episódios súbitos, recorrentes e reversíveis de fraqueza da musculatura esquelética desencadeados por situações de conteúdo emocional. Os sintomas acessórios são alucinações hipnagógicas, paralisia do sono e sono fragmentado. Critérios de diagnóstico clínico de acordo com a Classificação Internacional dos Transtornos do Sono são de sonolência excessiva e cataplexia. Recomenda-se a realização de polissonografia seguida do teste de latência múltipla do sono em um laboratório de sono para confirmação e diagnóstico de comorbidades. Quando não houver cataplexia, deve haver duas ou mais sonecas com sono REM no teste de latência múltipla do sono. Tipagem HLA-DQB1*0602 positiva com níveis de hipocretina-1 abaixo de 110pg/mL devem estar presentes para o diagnóstico de narcolepsia sem cataplexia e sem sonecas com sono REM.

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Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for Pharmacological Treatment

et al. 2017

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Narcolepsy type 1 (NT1) is a rare sleep disorder caused by the very specific loss of hypothalamic hypocretin (Hcrt)/orexin neurons. The exact underlying process leading to this destruction is yet unknown, but indirect evidence strongly supports an autoimmune origin. The association with immune-related genetic factors, in particular the strongest association ever reported in a disease with an allele of a human leukocyte antigen (HLA) gene, and with environmental factors (i.e., the H1N1 influenza infection and vaccination during the pandemic in 2009) are in favor of such a hypothesis. The loss of Hcrt neurons is irreversible, and NT1 is currently an incurable and disabling condition. Patients are managed with symptomatic medication, targeting the main symptoms (excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep), and they require a lifelong treatment. Improved diagnostic tools, together with an increased understanding of the pathogenesis of NT1, may lead to new therapeutic and even preventive interventions. One future treatment could include Hcrt replacement, but this neuropeptide does not cross the blood-brain barrier. However, Hcrt receptor agonists may be promising candidates to treat NT1. Another option is immune-based therapies, administered at disease onset, with already some initiatives to slow down or stop the dysimmune process. Whether immune-based therapy could be beneficial in NT1 remains, however, to be proven.

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Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB11501-DQB10602 haplotype

Cited by 24 publications

References 12 publications

An approach based on a genome-wide association study reveals candidate loci for narcolepsy

An approach based on a genome-wide association study reveals candidate loci for narcolepsy

Diretrizes brasileiras para o diagnóstico de narcolepsia

Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for Pharmacological Treatment

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