发作性睡病家族中人类白细胞抗原和肿瘤坏死因子-α基因的单倍型分析。

Haplotype analyses with the human leucocyte antigen and tumour necrosis factor-alpha genes in narcolepsy families.

作者信息

Hohjoh H, Terada N, Miki T, Honda Y, Tokunaga K

机构信息

Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Japan.

出版信息

Psychiatry Clin Neurosci. 2001 Feb;55(1):37-9. doi: 10.1046/j.1440-1819.2001.00782.x.

DOI:10.1046/j.1440-1819.2001.00782.x

PMID:11235856

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)-DRB11501 with the disorder. To understand the relationship of DRB11501 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 DRB11501-TNF-alpha(-857C) haplotype but also the DRB11501-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.

摘要

我们之前的研究表明，启动子区域第-857位存在胸腺嘧啶残基的肿瘤坏死因子-α基因[TNF-α(-857T)]可能与人类发作性睡病相关，而不依赖于人类白细胞抗原(HLA)-DRB11501与该疾病的强关联。为了了解发作性睡病患者中DRB11501与TNF-α(-857T)的关系，我们调查了四个日本发作性睡病家族的28名成员，并确定了这些成员中HLA-B、TNF-α(-857C/T)和HLA-DRB1的单倍型。所得单倍型表明，不仅DRB11501-TNF-α(-857C)单倍型，而且DRB11501-TNF-α(-857T)单倍型（在健康个体中罕见，可能对该疾病有很强的易感性）在患病成员中也存在。从少数成员中观察到的染色体重组情况来看，染色体重组可能在罕见的DRB1*1501-TNF-α(-857T)单倍型的产生中起作用。