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.
Gregory
Simon G
SG
Center for Human Genetics, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Schmidt
Silke
S
Seth
Puneet
P
Oksenberg
Jorge R
JR
Hart
John
J
Prokop
Angela
A
Caillier
Stacy J
SJ
Ban
Maria
M
Goris
An
A
Barcellos
Lisa F
LF
Lincoln
Robin
R
McCauley
Jacob L
JL
Sawcer
Stephen J
SJ
Compston
D A S
DA
Dubois
Benedicte
B
Hauser
Stephen L
SL
Garcia-Blanco
Mariano A
MA
Pericak-Vance
Margaret A
MA
Haines
Jonathan L
JL
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