title: A Single Nucleotide Polymorphism in the Il17ra Promoter Is Associated with Functional Severity of Ankylosing Spondylitis.
abstract: The aim of this study was to identify new genetic variants associated with the severity of ankylosing spondylitis (AS). We sequenced the exome of eight patients diagnosed with AS, selected on the basis of the severity of their clinical parameters. We identified 27 variants in exons and regulatory regions. The contribution of candidate variants found to AS severity was validated by genotyping two Spanish cohorts consisting of 180 cases/300 controls and 419 cases/656 controls. Relationships of SNPs and clinical variables with the Bath Ankylosing Spondylitis Disease Activity and Functional Indices BASDAI and BASFI were analyzed. BASFI was standardized by adjusting for the duration of the disease since the appearance of the first symptoms. Refining the analysis of SNPs in the two cohorts, we found that the rs4819554 minor allele G in the promoter of the IL17RA gene was associated with AS (p<0.005). This variant was also associated with the BASFI score. Classifying AS patients by the severity of their functional status with respect to BASFI/disease duration of the 60th, 65th, 70th and 75th percentiles, we found the association increased from p60 to p75 (cohort 1: p<0.05 to p<0.01; cohort 2: p<0.01 to p<0.005). Our findings indicate a genetic role for the IL17/ILRA axis in the development of severe forms of AS.
authors.affiliation: Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Jose Ramón
authors.initials: JR
authors.lastname: Vidal-Castiñeira
authors.affiliation: Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Vázquez
authors.affiliation: Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.|Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Diaz-Peña
authors.affiliation: Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Diaz-Bulnes
authors.affiliation: Department of Statistics, Hospital Universitario Central de Asturias, Oviedo, Spain.|Facultad de Ciencias de la Educación, Universidad Autónoma de Chile, Santiago de Chile, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Camblor
authors.affiliation: Molecular Genetics Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.affiliation: Dermatology II Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Coto-Segura
authors.affiliation: Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal.
authors.forename: Jacome
authors.initials: J
authors.lastname: Bruges-Armas
authors.affiliation: Rheumatology Service, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Pinto
authors.affiliation: Rheumatology Service, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain.
authors.forename: Francisco Jose
authors.initials: FJ
authors.lastname: Blanco
authors.affiliation: Rheumatology Service, Puerta del Hierro University Hospital, Majadahonda, Madrid.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Rheumatology Service, Puerta del Hierro University Hospital, Majadahonda, Madrid.
authors.forename: Juan
authors.initials: J
authors.lastname: Mulero
authors.affiliation: Rheumatology Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Queiro
authors.affiliation: Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.|Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez-Larrea
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D059472:Exome / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D053722:Receptors, Interleukin-17 / Q000235:genetics* / Q000502:physiology; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000235:genetics*
chemical_list: C109985:IL17RA protein, human; D053722:Receptors, Interleukin-17