DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe.

Détails

ID Serval
serval:BIB_0828CCB5A667
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe.
Périodique
Sleep
Auteur(s)
Tafti M., Hor H., Dauvilliers Y., Lammers G.J., Overeem S., Mayer G., Javidi S., Iranzo A., Santamaria J., Peraita-Adrados R., Vicario J.L., Arnulf I., Plazzi G., Bayard S., Poli F., Pizza F., Geisler P., Wierzbicka A., Bassetti C.L., Mathis J., Lecendreux M., Donjacour C.E., van der Heide A., Heinzer R., Haba-Rubio J., Feketeova E., Högl B., Frauscher B., Benetó A., Khatami R., Cañellas F., Pfister C., Scholz S., Billiard M., Baumann C.R., Ercilla G., Verduijn W., Claas F.H., Dubois V., Nowak J., Eberhard H.P., Pradervand S., Hor C.N., Testi M., Tiercy J.M., Kutalik Z.
ISSN
1550-9109 (Electronic)
ISSN-L
0161-8105
Statut éditorial
Publié
Date de publication
2014
Volume
37
Numéro
1
Pages
19-25
Langue
anglais
Résumé
STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects.
DESIGN: Retrospective case-control study.
SETTING: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication.
PATIENTS AND PARTICIPANTS: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included.
MEASUREMENTS AND RESULTS: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified.
CONCLUSION: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.
Mots-clé
Autoimmunity, GWAS, H1N1 vaccination, genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/04/2014 8:44
Dernière modification de la notice
20/08/2019 13:30
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