IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations.
Multiple sclerosis (MS) is the most common chronic inflammatory neurologic disorder diagnosed in young adults and, due to its chronic course, is responsible for a substantial economic burden. MS is considered to be a multifactorial disease in which both genetic and environmental factors intervene. The well-established human leukocyte antigen (HLA) association does not completely explain the genetic impact on disease susceptibility. However, identification and validation of non-HLA-genes conferring susceptibility to MS has proven to be difficult probably because of the small individual contribution of each of these genes. Recently, associations with two single nucleotide polymorphisms (SNPs) in the IL2RA gene (rs12722489, rs2104286) and one SNP in the IL7RA gene (rs6897932) have been reported by several groups. These three SNPs were genotyped in a French and a German population of MS patients using the hME assay by the matrix-assisted laser desorption/ionization time of flight technology (Sequenom, San Diego, CA, USA). We show that these SNPs do contribute to the risk of MS in these two unrelated European MS patient populations with odds ratios varying from 1.1 to 1.5. The discovery and validation of new genetic risk factors in independent populations may help toward the understanding of MS pathogenesis by providing valuable information on biological pathways to be investigated.
Weber
F
F
Max Planck Institute of Psychiatry, Munich, Germany. fweber@mpipsykl.mpg.de
Fontaine
B
B
Cournu-Rebeix
I
I
Kroner
A
A
Knop
M
M
Lutz
S
S
Müller-Sarnowski
F
F
Uhr
M
M
Bettecken
T
T
Kohli
M
M
Ripke
S
S
Ising
M
M
Rieckmann
P
P
Brassat
D
D
Semana
G
G
Babron
M-C
MC
Mrejen
S
S
Gout
C
C
Lyon-Caen
O
O
Yaouanq
J
J
Edan
G
G
Clanet
M
M
Holsboer
F
F
Clerget-Darpoux
F
F
Müller-Myhsok
B
B
D000328:Adult; D000368:Aged; D005260:Female; D005602:France; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D020395:Receptors, Interleukin-7