Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis.

Abstract

OBJECTIVES:

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=4.88x10(-2), OR=1.11). When we compared ATA+ SSc cases with ATA- SSc, both SNPs, rs3093024 and rs968334, showed significant associations (p=2.89x10(-2), OR=1.13; p=1.69x10(-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=1.00x10(-4), OR=1.16) comparing with healthy controls.

CONCLUSIONS:

Our work confirms the association of CCR6 gene and ATA+ SSc patients.

• Authors: Eguzkine Ochoa, José-Ezequiel Martin, Shervin Assasi, Lorenzo Beretta, Patricia Carreira, Alfredo Guillén, Carmen Pilar Simeón, Eugénie Koumakis, Philippe Dieude, Yannick Allanore, Francisco J García-Hernández, Gerard Espinosa, Ivan Castellví, Jose Luis Trapiella, Luis Rodriguez, Miguel Ángel González-Gay, María Victoria Egurbide, Luis Sáez, Jose Luis Callejas-Rubio, Jose Antonio Vargas-Hitos, Nicolas Hunzelmann, Gabriela Riemekasten, Torsten Witte, Jörg H W Distler, Alexander Kreuter, Claudio Lunardi, Alessandro Santaniello, Filemon K Tan, Paul G Shiels, Ariane Herrick, Jane Worthington, Madelon C Vonk, Bobby P Koeleman, Timothy R D J Radstake, Maureen D Mayes, Javier Martin, Spanish Scleroderma Group
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2015 Jul-Aug Vol. 33 Issue 4 Suppl 91 Pg. S31-5 ISSN: 0392-856X [Print] Italy
• PMID: 26314374 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• Autoantibodies
• Biomarkers
• CCR6 protein, human
• Receptors, CCR6
• DNA Topoisomerases, Type I
• TOP1 protein, human

Topics

• Autoantibodies (blood)
• Biomarkers (blood)
• Case-Control Studies
• Chi-Square Distribution
• DNA Topoisomerases, Type I (immunology)
• Europe
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Receptors, CCR6 (genetics)
• Risk Factors
• Scleroderma, Systemic (blood, diagnosis, epidemiology, ethnology, genetics)
• United States (epidemiology)
• White People (genetics)