Validation of the CD6 and TNFRSF1A loci as risk factors for multiple sclerosis in Spain.
A recent meta-analysis of genome-wide association screens coupled to a replication exercise in a combined US/UK collection led to the identification of 4 single nucleotide polymorphisms (SNPs) in three gene loci, i.e. TNFRSF1A, CD6 and IRF8, as novel risk factors for multiple sclerosis with genome-wide level of significance. In the present study, using a combined all-Spain collection of 2515 MS patients and 2942 healthy controls, we demonstrate significant association of rs17824933 in CD6 (P(CMH)=0.004; OR=1.14; 95% CI 1.04-1.24) and of rs1860545 in TNFRSF1A (P(CMH)=0.001; OR=1.15; 95% CI 1.06-1.25) with MS, while the low-frequency coding non-synonymous SNP rs4149584 in TNFRSF1A displayed a trend for association (P(CMH)=0.062; OR=1.27; 95% CI 0.99-1.63). This data reinforce a generic role for CD6 and TNFRSF1A in susceptibility to MS, extending to populations of southern European ancestry.
Swaminathan
Bhairavi
B
Neurogenomiks Laboratory, University of the Basque Country (UPV/EHU), Leioa, Spain.
Matesanz
Fuencisla
F
Cavanillas
Mariá L
ML
Alloza
Iraide
I
Otaegui
David
D
Olascoaga
Javier
J
Cénit
María C
MC
de las Heras
Virgina
V
Barcina
María García
MG
Arroyo
Rafael
R
Alcina
Antonio
A
Fernandez
Oscar
O
Antigüedad
Alfredo
A
Urcelay
Elena
E
Vandenbroeck
Koen
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D056426:Genetic Loci / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human