title: A cytokine gene screen uncovers SOCS1 as genetic risk factor for multiple sclerosis.
abstract: Cytokine and cytokine receptor genes, including IL2RA, IL7R and IL12A, are known risk factors for multiple sclerosis (MS). Excitotoxic oligodendroglial death mediated by glutamate receptors contributes to demyelinating reactions. In the present study, we screened 368 single-nucleotide polymorphisms (SNPs) in 55 genes or gene clusters coding for cytokines, cytokine receptors, suppressors of cytokine signaling (SOCS), complement factors and glutamate receptors for association with MS in a Spanish-Basque resident population. Top-scoring SNPs were found within or nearby the genes coding for SOCS-1 (P=0.0005), interleukin-28 receptor, alpha chain (P=0.0008), oncostatin M receptor (P=0.002) and interleukin-22 receptor, alpha 2 (IL22RA2; P=0.003). The SOCS1 rs243324 variant was validated as risk factor for MS in a separate cohort of 3919 MS patients and 4003 controls (combined Cochran-Mantel-Haenszel P=0.00006; odds ratio (OR)=1.13; 95% confidence interval (CI)=1.07-1.20). In addition, the T allele of rs243324 was consistently increased in relapsing-remitting/secondary progressive versus primary-progressive MS patients, in each of the six data sets used in this study (P(CMH)=0.0096; OR=1.24; 95% CI 1.05-1.46). The association with SOCS1 appears independent from the chr16MS risk locus CLEC16A.
authors.affiliation: Neurogenomiks Laboratory, Department of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain. k.vandenbroeck@ikerbasque.org
authors.forename: K
authors.initials: K
authors.lastname: Vandenbroeck
authors.forename: J
authors.initials: J
authors.lastname: Alvarez
authors.forename: B
authors.initials: B
authors.lastname: Swaminathan
authors.forename: I
authors.initials: I
authors.lastname: Alloza
authors.forename: F
authors.initials: F
authors.lastname: Matesanz
authors.forename: E
authors.initials: E
authors.lastname: Urcelay
authors.forename: M
authors.initials: M
authors.lastname: Comabella
authors.forename: A
authors.initials: A
authors.lastname: Alcina
authors.forename: M
authors.initials: M
authors.lastname: Fedetz
authors.forename: M A
authors.initials: MA
authors.lastname: Ortiz
authors.forename: G
authors.initials: G
authors.lastname: Izquierdo
authors.forename: O
authors.initials: O
authors.lastname: Fernandez
authors.forename: N
authors.initials: N
authors.lastname: Rodriguez-Ezpeleta
authors.forename: C
authors.initials: C
authors.lastname: Matute
authors.forename: S
authors.initials: S
authors.lastname: Caillier
authors.forename: R
authors.initials: R
authors.lastname: Arroyo
authors.forename: X
authors.initials: X
authors.lastname: Montalban
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: A
authors.initials: A
authors.lastname: Antigüedad
authors.forename: A
authors.initials: A
authors.lastname: Aransay
mesh_terms: D000328:Adult; D002885:Chromosomes, Human, Pair 16; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012307:Risk Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D037181:Lectins, C-Type; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins