Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis.
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 alpha chain (IL7Ralpha), 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 IL7Ralpha and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis.
Lundmark
Frida
F
Division of Neurology, Department of Clinical Neuroscience, Karolinska Institutet at Karolinska University Hospital-Huddinge, SE-141 86 Stockholm, Sweden.
Duvefelt
Kristina
K
Iacobaeus
Ellen
E
Kockum
Ingrid
I
Wallström
Erik
E
Khademi
Mohsen
M
Oturai
Annette
A
Ryder
Lars P
LP
Saarela
Janna
J
Harbo
Hanne F
HF
Celius
Elisabeth G
EG
Salter
Hugh
H
Olsson
Tomas
T
Hillert
Jan
J
D000328:Adult; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D005387:Finland; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000235:genetics*; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013548:Sweden
D015851:Interleukin-7; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain