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

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

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

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-HitosNicolas 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,

Infection & Immunity

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	S31-5
Journal	Clinical and Experimental Rheumatology
Volume	33
Issue number	4 Suppl 91
Publication status	Published - 1 Sept 2015

Keywords

Autoantibodies
Biomarkers
Case-Control Studies
Chi-Square Distribution
DNA Topoisomerases, Type I
Europe
European Continental Ancestry Group
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide
Receptors, CCR6
Risk Factors
Scleroderma, Systemic
United States
Meta-Analysis

Cite this

Ochoa, E., Martin, J.-E., Assasi, S., Beretta, L., Carreira, P., Guillén, A., Simeón, C. P., Koumakis, E., Dieude, P., Allanore, Y., García-Hernández, F. J., Espinosa, G., Castellví, I., Trapiella, J. L., Rodriguez, L., González-Gay, M. Á., Egurbide, M. V., Sáez, L., Callejas-Rubio, J. L. (2015). Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis. Clinical and Experimental Rheumatology, 33(4 Suppl 91), S31-5.

@article{33dc8fe75dde447bab564bfd29672dc1,

title = "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.",

keywords = "Autoantibodies, Biomarkers, Case-Control Studies, Chi-Square Distribution, DNA Topoisomerases, Type I, Europe, European Continental Ancestry Group, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Receptors, CCR6, Risk Factors, Scleroderma, Systemic, United States, Meta-Analysis",

author = "Eguzkine Ochoa and Jos{\'e}-Ezequiel Martin and Shervin Assasi and Lorenzo Beretta and Patricia Carreira and Alfredo Guill{\'e}n and Sime{\'o}n, {Carmen Pilar} and Eug{\'e}nie Koumakis and Philippe Dieude and Yannick Allanore and Garc{\'i}a-Hern{\'a}ndez, {Francisco J} and Gerard Espinosa and Ivan Castellv{\'i} and Trapiella, {Jose Luis} and Luis Rodriguez and Gonz{\'a}lez-Gay, {Miguel {\'A}ngel} and Egurbide, {Mar{\'i}a Victoria} and Luis S{\'a}ez and Callejas-Rubio, {Jose Luis} and Vargas-Hitos, {Jose Antonio} and Nicolas Hunzelmann and Gabriela Riemekasten and Torsten Witte and Distler, {J{\"o}rg H W} and Alexander Kreuter and Claudio Lunardi and Alessandro Santaniello and Tan, {Filemon K} and Shiels, {Paul G} and Ariane Herrick and Jane Worthington and Vonk, {Madelon C} and Koeleman, {Bobby P} and Radstake, {Timothy R D J} and Mayes, {Maureen D} and Javier Martin",

year = "2015",

month = sep,

day = "1",

language = "English",

volume = "33",

pages = "S31--5",

journal = "Clinical and Experimental Rheumatology",

issn = "0392-856X",

publisher = "Clinical and Experimental Rheumatology S.A.S.",

number = "4 Suppl 91",

}

Ochoa, E, Martin, J-E, Assasi, S, Beretta, L, Carreira, P, Guillén, A, Simeón, CP, Koumakis, E, Dieude, P, Allanore, Y, García-Hernández, FJ, Espinosa, G, Castellví, I, Trapiella, JL, Rodriguez, L, González-Gay, MÁ, Egurbide, MV, Sáez, L, Callejas-Rubio, JL, Vargas-Hitos, JA, Hunzelmann, N, Riemekasten, G, Witte, T, Distler, JHW, Kreuter, A, Lunardi, C, Santaniello, A, Tan, FK, Shiels, PG, Herrick, A, Worthington, J, Vonk, MC, Koeleman, BP, Radstake, TRDJ, Mayes, MD, Martin, J 2015, 'Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis', Clinical and Experimental Rheumatology, vol. 33, no. 4 Suppl 91, pp. S31-5.

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 - Assasi, 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, Miguel Ángel

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

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - Autoantibodies

KW - Biomarkers

KW - Case-Control Studies

KW - Chi-Square Distribution

KW - DNA Topoisomerases, Type I

KW - Europe

KW - European Continental Ancestry Group

KW - Gene Frequency

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Humans

KW - Odds Ratio

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Receptors, CCR6

KW - Risk Factors

KW - Scleroderma, Systemic

KW - United States

KW - Meta-Analysis

M3 - Article

C2 - 26314374

SN - 0392-856X

VL - 33

SP - S31-5

JO - Clinical and Experimental Rheumatology

JF - Clinical and Experimental Rheumatology

IS - 4 Suppl 91

ER -

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

Abstract

Keywords

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