title: IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk.
abstract: A recent genome-wide scan of nonsynonymous SNPs and ulterior validation in case-control and family analyses evidenced a susceptibility locus for type 1 diabetes (T1D) on chromosome 2q24.3. We aimed at testing the effect of this locus in other autoimmune diseases with complex genetic background, such as multiple sclerosis (MS). Four SNPs along the locus, rs13422767, rs2111485, rs1990760 and rs2068330, were genotyped using TaqMan MGB chemistry in 311 T1D and 412 MS patients and 535 ethnically matched healthy controls. The previously reported association of this locus was found for the first time in MS (rs2068330, G vs C: P=0.001; OR (95% CI)=0.73 (0.6-0.88)) and a trend for replication was observed in our Spanish diabetic cohort. Therefore, genes included in this locus - IFIH1 interferon induced helicase, GCA grancalcin or the potassium channel KCNH7 - are potential candidates implicated in the pathogenesis of these autoimmune diseases, although strong linkage disequilibrium in the region hampered further localization of the etiologic gene.
authors.affiliation: Department of Immunology, Hospital Universitario San Carlos, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
authors.forename: José Luis
authors.initials: JL
authors.lastname: Santiago
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Cénit
authors.forename: Virginia
authors.initials: V
authors.lastname: de Las Heras
authors.forename: Hermenegildo
authors.initials: H
authors.lastname: de la Calle
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D051638:Ether-A-Go-Go Potassium Channels; C503121:GCA protein, human; C486376:KCNH7 protein, human; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1