New susceptibility variants to narcolepsy identified in HLA class II region.
Hum Mol Genet
; 24(3): 891-8, 2015 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-25256355
ABSTRACT
Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*0602. DQB1*0602 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*0602 are associated with narcolepsy. The strongest association was with DQB1*0601 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*0302 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*0602 heterozygous cases and controls revealed dominant protective effects of DQB1*0601 and DQB1*0501. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*0501, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genes, MHC Class II
/
Asian People
/
HLA-DP beta-Chains
/
HLA-DQ beta-Chains
/
Narcolepsy
Type of study:
Prognostic_studies
Limits:
Humans
Country/Region as subject:
Asia
Language:
En
Journal:
Hum Mol Genet
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2015
Type:
Article
Affiliation country:
Japan