Variation in interleukin 7 receptor a chain (IL7R) influences risk of multiple sclerosis

被引：363

作者：

Lundmark, Frida

Duvefelt, Kristina

Iacobaeus, Ellen

Kockum, Ingrid

Wallstroem, Erik

Khademi, Mohsen

Oturai, Annette

Ryder, Lars P.

Saarela, Janna

Harbo, Hanne F.

Celius, Elisabeth G.

Salter, Hugh

Olsson, Tomas

Hillert, Jan ^{[1
]}

机构：

[1] Karolinska Univ Hosp, Dept Clin Neurosci, Div Neurol, SE-14186 Stockholm, Sweden

[2] Karolinska Univ Hosp, Clin Res Ctr, Mutat Anal Facil, SE-14186 Huddinge, Sweden

[3] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Clin Neurosci, Neuroimmunol Unit, SE-17176 Stockholm, Sweden

[4] Copenhagen Univ Hosp, Rigshosp, Danish Multiple Sclerosis Res Ctr, DK-2100 Copenhagen, Denmark

[5] Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark

[6] Natl Publ Hlth Inst, Dept Mol Med, FI-00290 Helsinki, Finland

[7] Univ Oslo, Inst Immunol, N-0027 Oslo, Norway

[8] Ulleval Hosp, Dept Neurol, N-0407 Oslo, Norway

[9] AstraZeneca R&D, Dept Dis Biol, Pharmacogenom Sect, SE-15185 Sodertalje, Sweden

来源：

NATURE GENETICS | 2007年 / 39卷 / 09期

关键词：

D O I：

10.1038/ng2106

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Multiple sclerosis is a chronic, often disabling, disease of the central nervous system affecting more than 1 in 1,000 people in most western countries. The inflammatory lesions typical of multiple sclerosis show autoimmune features and depend partly on genetic factors. Of these genetic factors, only the HLA gene complex has been repeatedly confirmed to be associated with multiple sclerosis, despite considerable efforts. Polymorphisms in a number of non- HLA genes have been reported to be associated with multiple sclerosis, but so far confirmation has been difficult. Here, we report compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor a chain ( IL7R alpha), indeed contribute to the non- HLA genetic risk in multiple sclerosis, demonstrating a role for this pathway in the pathophysiology of this disease. In addition, we report altered expression of the genes encoding IL7R alpha and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis.

引用

页码：1108 / 1113

页数：6

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