Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis.
Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.
Center for Human Genetics, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Simon G
SG
Gregory
Silke
S
Schmidt
Puneet
P
Seth
Jorge R
JR
Oksenberg
John
J
Hart
Angela
A
Prokop
Stacy J
SJ
Caillier
Maria
M
Ban
An
A
Goris
Lisa F
LF
Barcellos
Robin
R
Lincoln
Jacob L
JL
McCauley
Stephen J
SJ
Sawcer
D A S
DA
Compston
Benedicte
B
Dubois
Stephen L
SL
Hauser
Mariano A
MA
Garcia-Blanco
Margaret A
MA
Pericak-Vance
Jonathan L
JL
Haines
D000328:Adult; D017398:Alternative Splicing; D000818:Animals; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D005060:Europe; D005192:Family Health; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006367:HeLa Cells; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D014162:Transfection; D014481:United States
D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain