Skip to main content
Log in

Distribution of HLA-DQB1 in Czech Patients with Central Hypersomnias

  • Original Article
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

The aim of our study was to analyze the distribution of HLA-DQB1 in Czech patients with central hypersomnias and differences between diagnostic groups of narcolepsy type 1 (NT1), type 2 (NT2), idiopathic hypersomnia (IH) and no central hypersomnia subjects (no-CH). Statistical analysis of DQB1 genotyping was performed on the cohort of 716 patients (375 men, 341 women) with reported excessive daytime sleepiness. DQB1*06:02 allele was present in 94% of the NT1 patients. The decrease of DQB1*06:03 allele was also confirmed. No other DQB1*06 allele nor any other DQB1 allele group was differently distributed in the NT1. In the cohort of NT2 patients DQB1*06:02 allele was present in 43%. Allele group DQB*05 was detected with a significantly higher frequency in this diagnostic unit. Any differences in presence of DQB1*05 alleles in NT2 patients were not reported so far. The cohort of patients with IH did not show any difference in allele distribution of DQB1 alleles/allele groups comparing to healthy controls. DQB1*06:02 allele was significantly increased in the no hypersomnia group. No other DQB1 allele/allele group had any difference in distribution in patients comparing to healthy controls. The different distribution of DQB1*06:02 and other DQB1 alleles/allele groups was detected in analyzed diagnostic groups. These results indicate that DQB1 contributes to the genetic predisposition to NT1, NT2, IH and no-CH in different manners.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • American Academy of Sleep Medicine (2014) The international classification of sleep disorders, 3rd edn (ICSD-3). ISBN 978-0991543410. http://www.esst.org/adds/ICSD.pdf. Accessed 29 Aug 2014

  • Anderson KN, Pilsworth S, Sharples LD et al (2007) Idiopathic hypersomnia: a study of 77 cases. Sleep 30:1274–1281

    Article  PubMed  PubMed Central  Google Scholar 

  • Andlauer O, Moore H 4th, Hong SC et al (2012) Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy. Sleep 35:1247–1255

    PubMed  PubMed Central  Google Scholar 

  • Aran A, Lin L, Nevsimalova S et al (2009) Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep 32:979–983

    PubMed  PubMed Central  Google Scholar 

  • Berkowski JA, Shelgikar AV (2016) Disorders of excessive daytime sleepiness including narcolepsy and idiopathic hypersomnia. Sleep Med Clin 11:365–378

    Article  PubMed  Google Scholar 

  • Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58:882–893

    Article  PubMed  Google Scholar 

  • DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  • Dobrovolna M, Jiraskova K, Sonka K et al (2007) HLA association with narcolepsy in Czech patients. Abstracts for the 21st European Immunogenetics and Histocompatibility Conference, Barcelona, Spain, May 5–8, 2007. Tissue Antigens 69:373–532

    Article  Google Scholar 

  • Fleiss JL (1981) Statistical methods for rates and proportions, 2nd edn. Wiley, New York

    Google Scholar 

  • Goel N, Banks S, Mignot E et al (2010) DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness and fatigue. Neurology 75:1509–1519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Galarza FF, Takeshita LY et al (2015) Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acid Res 43:D784–D788

    Article  PubMed  Google Scholar 

  • Han F, Lin L, Li J et al (2012) HLA-DQ association and allele competition in Chinese narcolepsy. Tissue Antigens 80:328–335

    Article  CAS  PubMed  Google Scholar 

  • Heidbreder A, Frauscher B et al (2016) Not only sleepwalking but NREM parasomnia irrespective of the type is associated with HLA DQB1*05:01. J Clin Sleep Med 12:565–570

    Article  PubMed  PubMed Central  Google Scholar 

  • Hohjoh H, Terada N, Honda Y et al (2001) Negative association of the HLA-DRB1*1502-DQB1*0601 haplotype with human narcolepsy. Immunogenetics 52:299–301

    Article  CAS  PubMed  Google Scholar 

  • Hong SC, Lin L et al (2007) DQB1*0301 and DQB1*0601 modulate narcolepsy susceptibility in Koreans. Hum Immunol 68:59–68

    Article  CAS  PubMed  Google Scholar 

  • Hor H, Kutalik Z et al (2010) Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nat Genet 42:786–789

    Article  CAS  PubMed  Google Scholar 

  • Lecendreux M, Bassetti C et al (2003) HLA and genetic susceptibility to sleepwalking. Mol Psychiatry 8:114–117

    Article  CAS  PubMed  Google Scholar 

  • Liblau RS, Vassalli A, Seifinejad A et al (2015) Hypocretin (orexin) biology and the pathology of narcolepsy with cataplexy. Lancet Neurol 14:318–328

    Article  CAS  PubMed  Google Scholar 

  • Lin L, Hungs M, Mignot E (2001) Narcolepsy and the HLA region. J Neuroimmunol 117:9–20

    Article  CAS  PubMed  Google Scholar 

  • Littner MR, Kushida C et al (2005) Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep 28:113–121

    PubMed  Google Scholar 

  • Martins-da-Silva A, Lopes J et al (2014) Usefulness of genetic characterization of narcolepsy and hypersomnia on phenotype definition: a study in Portuguese patients. Rev Neurol 58:49–54

    PubMed  Google Scholar 

  • Maski K, Owens JA (2016) Insomnia, parasomnias, and narcolepsy in children: clinical features, diagnosis, and management. Lancet Neurol 15:1170–1181

    Article  PubMed  Google Scholar 

  • Mignot E, Lin X, Arrigoni J et al (1994) DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans. Sleep 17:60–67

    Article  Google Scholar 

  • Mignot E, Hayduk R, Grumet FC et al (1997) HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients. Sleep 20:1012–1020

    CAS  PubMed  Google Scholar 

  • Mignot E, Young T, Lin L et al (1998) Reduction of REM sleep latency associated with HLA-DQB1*0602 in normal adults. Lancet 351:727

    Article  CAS  PubMed  Google Scholar 

  • Mignot E, Young T et al (1999) Nocturnal sleep and daytime sleepiness in normal subjects with HLA-DQB1*0602. Sleep 22:347–352

    CAS  PubMed  Google Scholar 

  • Mignot E, Lin L et al (2001) Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Genet 68:686–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mignot E, Lammers GJ et al (2002) The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 59:1553–1562

    Article  PubMed  Google Scholar 

  • Miyagawa T, Toyoda H et al (2015) An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population. Hum Genome Var 2:15031

    Article  PubMed  PubMed Central  Google Scholar 

  • Nishino S, Okura M, Mignot E (2000) Narcolepsy: genetic predisposition and neuropharmacological mechanisms. Review article. Sleep Med Rev 4:57–99

    Article  PubMed  Google Scholar 

  • Noble WS (2009) How does multiple testing correction work? Nat Biotechnol 27:1135–1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Partinen M, Kornum BR et al (2014) Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol 13:600–613

    Article  CAS  PubMed  Google Scholar 

  • Pelin Z, Guilleminault C, Risch N et al (1998) HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups: US Modafinil in Narcolepsy Multicenter Study Group. Tissue Antigens 51:96–100

    Article  CAS  PubMed  Google Scholar 

  • Peyron C, Faraco J et al (2000) A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6:991–997

    Article  CAS  PubMed  Google Scholar 

  • Robinson J, Halliwell JA et al (2015) The IPD and IPD-IMGT/HLA Database: allele variant databases. Nucleic Acids Res 43:D423–D431

    Article  PubMed  Google Scholar 

  • Roth B, Nevsimalova S et al (1985) A study of the occurrence of HLA DR2 in 124 narcoleptics: clinical aspects. Schweizer Arch Neurol Psychiatr 139:41–51

    Google Scholar 

  • Sonka K, Pazderova L et al (2014) The value of repeated non-confirmatory multiple sleep latency test (MSLT) for the diagnosis of narcolepsy. Cesk Slov Neurol 77(110):444–448

    Google Scholar 

  • Tafti M, Hor H et al (2014) DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. Sleep 37:19–25

    PubMed  PubMed Central  Google Scholar 

  • Tate MW, Brown SM (1970) Note on the Cochran Q test. J Am Statistical Assoc 329:155–160

    Article  Google Scholar 

  • Trotti LM, Staab BA, Rye DB (2013) Test-retest reliability of the multiple sleep latency test in narcolepsy without cataplexy and idiopathic hypersomnia. J Clin Sleep Med 9:789–795

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the project Ministry of Health, Czech Republic (00023736, IHBT).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Milena Vrana.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vrana, M., Siffnerova, V., Pecherkova, P. et al. Distribution of HLA-DQB1 in Czech Patients with Central Hypersomnias. Arch. Immunol. Ther. Exp. 64 (Suppl 1), 89–98 (2016). https://doi.org/10.1007/s00005-016-0435-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-016-0435-5

Keywords

Navigation