PMID- 10488740
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20190826
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 54
IP  - 2
DP  - 1999 Aug
TI  - Significant association of a single nucleotide polymorphism in the tumor necrosis 
      factor-alpha (TNF-alpha) gene promoter with human narcolepsy.
PG  - 138-45
AB  - Narcolepsy is a sleep disorder in which multiple factors, including environmental 
      and genetic factors, are involved. A genetic factor strongly associated with the 
      disorder has been found in the human leukocyte antigen (HLA) class II region: the 
      haplotype, DRB1*1501-DQB1*0602, predisposes to narcolepsy. No susceptibility 
      genes other than the HLA-haplotype have been found. In this paper, we performed 
      an association study of the tumor necrosis factor-alpha (TNF-alpha) gene located 
      in the HLA class III region with human narcolepsy, in which we examined the known 
      single-nucleotide polymorphisms (SNPs) in the promoter region in 49 narcoleptic 
      patients, who were all positive for DRBI*1501, and 111 healthy control 
      individuals. The results indicated that the frequency of the genotype at position 
      -857 (-857SNP) was significantly different between the patients and controls, and 
      the allele frequencies of 857SNP revealed that the frequency of -857T was 
      significantly increased in the patients as compared with that in the controls 
      (P=0.0068). In addition, haplotypes presumed from HLA-DRB1, -857SNP and HLA-B 
      loci suggested that -857T was mainly associated with DRB1 alleles other than 
      DRB1*1501: the significant increase in frequency of -857T in the patients was not 
      caused by allelic association with DRB1*1501. Therefore, it is conceivable that 
      the TNF-alpha with 857T was associated with narcolepsy independently of the 
      strong association of DRB1*1501 with the disorder. Altogether, the data presented 
      here lead us to propose that TNF-alpha could be a new susceptibility gene in 
      human narcolepsy.
FAU - Hohjoh, H
AU  - Hohjoh H
AD  - Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 
      Japan. hohjohh@m.tokyo.ac.jp
FAU - Nakayama, T
AU  - Nakayama T
FAU - Ohashi, J
AU  - Ohashi J
FAU - Miyagawa, T
AU  - Miyagawa T
FAU - Tanaka, H
AU  - Tanaka H
FAU - Akaza, T
AU  - Akaza T
FAU - Honda, Y
AU  - Honda Y
FAU - Juji, T
AU  - Juji T
FAU - Tokunaga, K
AU  - Tokunaga K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (Nucleotides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Alleles
MH  - Female
MH  - Histocompatibility Testing
MH  - Humans
MH  - Male
MH  - Narcolepsy/*genetics
MH  - Nucleotides/*genetics/isolation & purification
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Genetic/*genetics
MH  - Polymorphism, Restriction Fragment Length
MH  - Polymorphism, Single-Stranded Conformational
MH  - Promoter Regions, Genetic/*genetics
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - 10.1034/j.1399-0039.1999.540204.x [doi]
PST - ppublish
SO  - Tissue Antigens. 1999 Aug;54(2):138-45. doi: 10.1034/j.1399-0039.1999.540204.x.