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Published on: June 1, 2014
Haplotype analyses with the human leucocyte antigen and tumour necrosis factor-alpha genes in narcolepsy families
1Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Japan. hohjohn@m.u-tokyo.ac.jp
Abstract:
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.
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