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首页> 外文期刊>Psychiatric genetics >A rare form of narcolepsy (HLA-DR2-) shows possible association with (functionally relevant) alpha-interferon gene polymorphisms.
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A rare form of narcolepsy (HLA-DR2-) shows possible association with (functionally relevant) alpha-interferon gene polymorphisms.

机译:发作性睡病(HLA-DR2-)的一种罕见形式显示可能与(功能相关)α-干扰素基因多态性相关。

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摘要

Narcolepsy is a neuropsychiatric disease caused by complex disturbance of sleep regulation. The main symptoms comprise daytime sleepiness and cataplexy. Although the aetiology remains unclear so far, narcolepsy is genetically characterized by strong linkage to the human leukocyte antigen complex as more than 90% of the patients are typed HLA-DR2+. Recently, it has become apparent that the orexin (hypocretin) neurotransmitter system plays a key role in the pathogenesis of the disease. Canine narcolepsy is caused by mutations in the orexin receptor 2 gene, and narcoleptic patients show specifically decreased cerebrospinal fluid orexin levels. Decreased promotor activity of the prepro-orexin gene is caused by binding of alpha-interferon in vitro. To investigate the possible role of IFNA gene polymorphisms in the pathogenesis of narcolepsy, we have genotyped two single nucleotide polymorphisms in IFNA genes as well as a neighbouring microsatellite. No association was evident in the prevalent DR2+ group. Yet, the IFNA10 single nucleotide polymorphisms and the IFNA microsatellite are associated with the DR2- patient group. Thus, the pathogenetic role of interferons needs to be defined in DR2- narcolepsy.
机译:发作性睡病是一种神经精神疾病,由复杂的睡眠调节障碍引起。主要症状包括白天嗜睡和瘫痪。尽管至今病因尚不清楚,但由于90%以上的患者为HLA-DR2 +型,故发作性睡病的遗传学特征是与人白细胞抗原复合物的牢固连接。最近,很明显,食欲素(hypocretin)神经递质系统在该疾病的发病机理中起关键作用。犬性发作性睡病是由orexin受体2基因的突变引起的,并且发作性癫痫患者显示出脑脊液中orexin含量特别降低。前原毒素基因的启动子活性降低是由体外α-干扰素的结合引起的。为了研究发作性睡病发病机理中IFNA基因多态性的可能作用,我们对IFNA基因中的两个单核苷酸多态性以及附近的微卫星进行了基因分型。在流行的DR2 +组中没有明显的关联。但是,IFNA10单核苷酸多态性和IFNA微卫星与DR2患者组有关。因此,在DR2-嗜睡症中需要确定干扰素的致病作用。

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