TY - JOUR
T1 - Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis
AU - Ochoa, Eguzkine
AU - Martin, José Ezequiel
AU - Assassi, Shervin
AU - Beretta, Lorenzo
AU - Carreira, Patricia
AU - Guillén, Alfredo
AU - Simeón, Carmen Pilar
AU - Koumakis, Eugénie
AU - Dieude, Philippe
AU - Allanore, Yannick
AU - García-Hernández, Francisco J.
AU - Espinosa, Gerard
AU - Castellví, Ivan
AU - Trapiella, Jose Luis
AU - Rodriguez, Luis
AU - González-Gay, Miguelángel
AU - Egurbide, María Victoria
AU - Sáez, Luis
AU - Callejas-Rubio, Jose Luis
AU - Vargas-Hitos, Jose Antonio
AU - Hunzelmann, Nicolas
AU - Riemekasten, Gabriela
AU - Witte, Torsten
AU - Distler, Jörg H.W.
AU - Kreuter, Alexander
AU - Lunardi, Claudio
AU - Santaniello, Alessandro
AU - Tan, Filemon K.
AU - Shiels, Paul G.
AU - Herrick, Ariane
AU - Worthington, Jane
AU - Vonk, Madelon C.
AU - Koeleman, Bobby P.
AU - Radstake, Timothy R.D.J.
AU - Mayes, Maureen D.
AU - Martin, Javier
AU - Ortego-Centeno, Norberto
AU - Ríos, Raquel
AU - Granada, Cecilio
AU - Camps, María Teresa
AU - Fernández-Nebro, Antonio
AU - Sánchez-Román, Julio
AU - Castillo, M. Jesús
AU - Aguirre, M. ángeles
AU - Gómez-Gracia, Inmaculada
AU - Fernández-Gutiérrez, Benjamín
AU - Vicente, Esther
AU - Andreu, José Luis
AU - De Castro, Mónica Fernández
AU - De la Peña, Paloma García
AU - López-Longo, Francisco Javier
AU - Martínez, Lina
AU - Fonollosa, Vicente
AU - Tolosa, Carlos
AU - Pros, Anna
AU - Carballeira, Mónica Rodríguez
AU - Rivas, Manel Rubio
AU - Santamaría, Vera Ortiz
AU - Madroñero, Ana Belén
AU - Díaz, Bernardino
AU - Freire, Mayka
AU - Sousa, Adrián
AU - Mateo, Patricia Fanlo
AU - Díaz, Federico
AU - Hernández, Vanesa
AU - Beltrán, Emma
AU - Grau, Elena
AU - Román-Ivorra, José Andrés
AU - Alegre Sancho, Juan José
AU - Blanco García, Francisco J.
AU - Oreiro, Natividad
N1 - Publisher Copyright:
© Clinical and Experimental Rheumatology 2015.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2015
Y1 - 2015
N2 - Objective. The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA+) production in SSc patients in a candidate gene study. This gene has been proposed to have a critical role in IL-17-driven autoimmunity in human diseases. Methods. In order to confirm the association between CCR6 and ATA+ SSc patients, we performed an independent replication study in populations of European ancestry. We studied two CCR6 genetic variants (rs968334 and rs3093024) in a total of 901 ATA+ SSc cases, 3,258 ATA- SSc cases and 7,865 healthy controls and compared allelic frequencies for those SNPs in ATA+ SSc with healthy controls and also with ATA- SSc patients. Results. The comparison performed between ATA+ SSc patients and healthy controls showed significant association with SNP rs968334 (p=4.88 x 10-2, OR=1.11). When we compared ATA+ SSc cases with ATA- SSc, both SNPs, rs3093024 and rs968334, showed significant associations (p=2.89 x 10-2, OR=1.13; p=1.69 x 10-2, OR=1.15). Finally, in order to increase even more sample size and statistical power, we meta-analysed our study with the previous reported and found a significant association between SNP rs3093024 and ATA+ SSc patients (p=1.00 x 10-4, OR=1.16) comparing with healthy controls. Conclusion. Our work confirms the association of CCR6 gene and ATA+ SSc patients.
AB - Objective. The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA+) production in SSc patients in a candidate gene study. This gene has been proposed to have a critical role in IL-17-driven autoimmunity in human diseases. Methods. In order to confirm the association between CCR6 and ATA+ SSc patients, we performed an independent replication study in populations of European ancestry. We studied two CCR6 genetic variants (rs968334 and rs3093024) in a total of 901 ATA+ SSc cases, 3,258 ATA- SSc cases and 7,865 healthy controls and compared allelic frequencies for those SNPs in ATA+ SSc with healthy controls and also with ATA- SSc patients. Results. The comparison performed between ATA+ SSc patients and healthy controls showed significant association with SNP rs968334 (p=4.88 x 10-2, OR=1.11). When we compared ATA+ SSc cases with ATA- SSc, both SNPs, rs3093024 and rs968334, showed significant associations (p=2.89 x 10-2, OR=1.13; p=1.69 x 10-2, OR=1.15). Finally, in order to increase even more sample size and statistical power, we meta-analysed our study with the previous reported and found a significant association between SNP rs3093024 and ATA+ SSc patients (p=1.00 x 10-4, OR=1.16) comparing with healthy controls. Conclusion. Our work confirms the association of CCR6 gene and ATA+ SSc patients.
UR - http://www.scopus.com/inward/record.url?scp=84946204707&partnerID=8YFLogxK
M3 - Journal articles
C2 - 26314374
AN - SCOPUS:84946204707
SN - 0392-856X
VL - 33
SP - 31
EP - 35
JO - Clinical and Experimental Rheumatology
JF - Clinical and Experimental Rheumatology
ER -