[Positivity analysis of human leukocyte histocompatibility antigen-DQB1*0602 allele in Chinese patients with narcolepsy].
OBJECTIVE
To explore the association of narcolepsy with human leukocyte histocompatibility antigen (HLA)-DQB1*0602 allele in Chinese narcoleptic patients and examine its relationship with different phenotypes.


METHODS
A total of 1 223 narcoleptic patients (NC, narcolepsy with typical cataplexy, n = 1 132; NWC, narcolepsy without cataplexy, n = 91) diagnosed at Sleep Center of Peking University People's Hospital from August 1998 to July 2011 were recruited into this retrospective study. According to the onset age, they were divided into early-onset group (onset age ≤ 15 y, n = 1 037) and late-onset group (onset age >15 y, n = 181). All of them underwent a polymerase chain reaction with specific sequence primer (PCR-SSP) HLA-DQB1*0602 typing. And the cerebrospinal fluid levels of hypocretin-1 (hcrt-1) were measured in 156 narcoleptic patients and they were divided into hcrt deficiency group (hcrt-1<138 ng/L, n = 115) and hcrt normal group (hcrt-1 ≥ 138 ng/L, n = 41). And 728 healthy volunteers were selected as control group. The expression positivity of HLA-DQB1*0602 gene was analyzed for each group.


RESULTS
There were 1 223 narcoleptic patients including 825 males (67.5%) and 398 females (32.5%) with an average age of (16.6 ± 12.6) years on visiting. There were 728 normal controls including 443 males (60.9%) and 285 females (39.1%) with an average age of (26.6 ± 11.4) years on blood sampling. The positive rate of HLA-DQB1*0602 in narcoleptic, NC and NWC groups was 94.7% (1 158/1 223), 97.0% (1 098/1 132) and 65.9% (60/91) respectively.NC group had a higher rate of HLA-DQB1*0602 positivity (χ² = 155.4, P = 0.000). Both groups were higher than that in control group of 19.5% (142/728). The positive rate of HLA-DQB1*0602 in early-onset group was 95.5% (990/1 037) versus 90.1% (163/181) in late-onset group (χ² = 9.25, P = 0.010). Among those with hcrt-1 measurement, 98.3% (113/115) were HLA-DQB1*0602 positive in hcrt deficiency narcolepsy group versus 25.6% (11/43) in hcrt non-deficiency group (χ² = 94.6, P = 0.001).


CONCLUSIONS
HLA-DQB1* 0602 is an important marker in this large sample of Chinese patients with narcolepsy.Its frequency is much higher in patients with cataplexy, early-onset age and hcrt-1 deficiency.
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Jing
J
Li
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China. Email: dongxs_2000@163.com.
Xiaosong
X
Dong
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Han
H
Yan
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Yanan
Y
Liu
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Pei
P
An
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Long
L
Zhao
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Qinghua
Q
Li
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Xiaozhe
X
Zhang
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Zhancheng
Z
Gao
Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Fang
F
Han
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000235:genetics*; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D000068797:Orexins; D055815:Young Adult
C000596229:HCRT protein, human; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins