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

摘要: STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously 5 variants, and 10 other potential a large European sample of subjects. DESIGN: Retrospective case-control study. SETTING: A recent study showed that over 76% significant genome-wide association lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, 30 single nucleotide polymorphisms (SNPs) P < 10(-4) mapping to DHSs. Ten SNPs tagging sites, HLADQB1, all reported significantly were for replication. PATIENTS AND PARTICIPANTS: For 1,261 patients 1,422 HLA-DQB1*06:02-matched controls included. HLA study, 1,218 3,541 MEASUREMENTS RESULTS: None top DHSs replicated. Out SNPs, only rs2858884 region (P 2x10(-9)) rs1154155 TRA locus 2x10(-8)) DQB1 typing confirmed DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds 0.17, DQB1*05:01, 0.56, DQB1*06:09 0.21, DQB1*02 0.76) also identified. CONCLUSION: An overwhelming portion is found at locus. Since positive subjects are 251-fold increase narcolepsy, cases after H1N1 vaccination this allele, genotyping may be relevant public health policy.