Haplotype analyses with the human leucocyte antigen and tumour necrosis factor-alpha genes in narcolepsy families.
Our previous study suggested that the tumour necrosis factor-alpha gene with thymine residue at position -857 in its promoter region [TNF-alpha(-857T)] could be associated with human narcolepsy independently of a strong association of the human leucocyte antigen (HLA)-DRB1*1501 with the disorder. To understand the relationship of DRB1*1501 with TNF-alpha(-857T) in narcoleptic patients, we investigated 28 members of four Japanese narcolepsy families and determined the haplotypes with the HLA-B, TNF-alpha(-857C/T) and HLA-DRB1 in the members. The resultant haplotypes indicated that not only the DRB1*1501-TNF-alpha(-857C) haplotype but also the DRB1*1501-TNF-alpha(-857T) haplotype, which is rare in healthy individuals and may have a strong predisposition to the disorder, were present in the affected members. From the chromosomal recombination observed in a few members, it is possible that chromosomal recombination could play a role in the generation of the rare DRB1*1501-TNF-alpha(-857T) haplotype.
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Japan. hohjohn@m.u-tokyo.ac.jp
H
H
Hohjoh
N
N
Terada
T
T
Miki
Y
Y
Honda
K
K
Tokunaga
D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D009290:Narcolepsy / Q000235:genetics*; D010375:Pedigree; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha