Influence of the IL6 gene in susceptibility to systemic sclerosis

Maria Carmen Cénit; Carmen P. Simeón; Madelon C. Vonk; Jose L. Callejas-Rubio; Gerard Espinosa; Patricia Carreira; Francisco J. Blanco; Javier Narvaez; Carlos Tolosa; José A. Román-Ivorra; Inmaculada Gómez-Garćia; Francisco J. García-Hernández; María Gallego; Rosa García-Portales; María Victoria Egurbide; Vicente Fonollosa; Paloma García De La Pẽna; Francisco J. López-Longo; Miguel A. González-Gay; Roger Hesselstrand; Gabriela Riemekasten; Witte Torsten; Alexandre E. Voskuyl; Annemie J. Schuerwegh; Rajan Madhok; Carmen Fonseca; Christopher Denton; Annika Nordin; Øyvind Palm; Jacob M. Van Laar; Nicolas Hunzelmann; Jörg H W Distler; Alexander Kreuter; Ariane Herrick; Jane Worthington; Bobby P. Koeleman; Timothy R D J Radstake; Javier Martiń; Norberto Ortego-Centeno; Raquel Ríos; Nuria Navarrete; María Teresa Camps; Antonio Fernández-Nebro; María F. González-Escribano; Julio Sánchez-Román; M. Jesús Castillo; M. Ángeles Aguirre; Benjamín Fernández-Gutiérrez; Luis Rodríguez-Rodríguez; Esther Vicente; José Luis Andreu; Mónica Fernández De Castro; Lina Martínez; Iván Castellví; Anna Pros; Mónica Rodríguez Carballeira; Raquel López Mejías; Bernardino Díaz; Luis Trapiella; María Del Carmen Freire; Inés Vaqueiro; Luis Sáez-Comet; Federico Díaz; Vanesa Hernández; Emma Beltrán; María Ángeles Robles; Natividad Oreiro

doi:10.3899/jrheum.120506

Influence of the IL6 gene in susceptibility to systemic sclerosis

Maria Carmen Cénit, Carmen P. Simeón, Madelon C. Vonk, Jose L. Callejas-Rubio, Gerard Espinosa, Patricia Carreira, Francisco J. Blanco, Javier Narvaez, Carlos Tolosa, José A. Román-Ivorra, Inmaculada Gómez-Garćia, Francisco J. García-Hernández, María Gallego, Rosa García-Portales, María Victoria Egurbide, Vicente Fonollosa, Paloma García De La Pẽna, Francisco J. López-Longo, Miguel A. González-Gay, Roger HesselstrandGabriela Riemekasten, Witte Torsten, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Rajan Madhok, Carmen Fonseca, Christopher Denton, Annika Nordin, Øyvind Palm, Jacob M. Van Laar, Nicolas Hunzelmann, Jörg H W Distler, Alexander Kreuter, Ariane Herrick, Jane Worthington, Bobby P. Koeleman, Timothy R D J Radstake, Javier Martiń, Norberto Ortego-Centeno, Raquel Ríos, Nuria Navarrete, María Teresa Camps, Antonio Fernández-Nebro, María F. González-Escribano, Julio Sánchez-Román, M. Jesús Castillo, M. Ángeles Aguirre, Benjamín Fernández-Gutiérrez, Luis Rodríguez-Rodríguez, Esther Vicente, José Luis Andreu, Mónica Fernández De Castro, Lina Martínez, Iván Castellví, Anna Pros, Mónica Rodríguez Carballeira, Raquel López Mejías, Bernardino Díaz, Luis Trapiella, María Del Carmen Freire, Inés Vaqueiro, Luis Sáez-Comet, Federico Díaz, Vanesa Hernández, Emma Beltrán, María Ángeles Robles, Natividad Oreiro

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

Abstract

Objective. Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology. Results. Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). Conclusion. Our results suggest that the IL6 gene may influence the development of SSc and its progression. The Journal of Rheumatology Copyright © 2012. All rights reserved.

Original language	English
Pages (from-to)	2294-2302
Number of pages	8
Journal	Journal of Rheumatology
Volume	39
Issue number	12
DOIs	https://doi.org/10.3899/jrheum.120506
Publication status	Published - Dec 2012

Keywords

Gene
Genetic Studies
IL6
Polymorphisms
Scleroderma
Systemic sclerosis

Access to Document

10.3899/jrheum.120506

http://www.jrheum.org/content/39/12/2294.full.pdf+html

Cite this

Cénit, M. C., Simeón, C. P., Vonk, M. C., Callejas-Rubio, J. L., Espinosa, G., Carreira, P., Blanco, F. J., Narvaez, J., Tolosa, C., Román-Ivorra, J. A., Gómez-Garćia, I., García-Hernández, F. J., Gallego, M., García-Portales, R., Egurbide, M. V., Fonollosa, V., De La Pẽna, P. G., López-Longo, F. J., González-Gay, M. A., ... Oreiro, N. (2012). Influence of the IL6 gene in susceptibility to systemic sclerosis. Journal of Rheumatology, 39(12), 2294-2302. https://doi.org/10.3899/jrheum.120506

@article{5cb73d497a4b4fc68edbf21d4d89dadb,

title = "Influence of the IL6 gene in susceptibility to systemic sclerosis",

abstract = "Objective. Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan{\textregistered} allele discrimination technology. Results. Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). Conclusion. Our results suggest that the IL6 gene may influence the development of SSc and its progression. The Journal of Rheumatology Copyright {\textcopyright} 2012. All rights reserved.",

keywords = "Gene, Genetic Studies, IL6, Polymorphisms, Scleroderma, Systemic sclerosis",

author = "C{\'e}nit, {Maria Carmen} and Sime{\'o}n, {Carmen P.} and Vonk, {Madelon C.} and Callejas-Rubio, {Jose L.} and Gerard Espinosa and Patricia Carreira and Blanco, {Francisco J.} and Javier Narvaez and Carlos Tolosa and Rom{\'a}n-Ivorra, {Jos{\'e} A.} and Inmaculada G{\'o}mez-Gar{\'c}ia and Garc{\'i}a-Hern{\'a}ndez, {Francisco J.} and Mar{\'i}a Gallego and Rosa Garc{\'i}a-Portales and Egurbide, {Mar{\'i}a Victoria} and Vicente Fonollosa and {De La Pẽna}, {Paloma Garc{\'i}a} and L{\'o}pez-Longo, {Francisco J.} and Gonz{\'a}lez-Gay, {Miguel A.} and Roger Hesselstrand and Gabriela Riemekasten and Witte Torsten and Voskuyl, {Alexandre E.} and Schuerwegh, {Annemie J.} and Rajan Madhok and Carmen Fonseca and Christopher Denton and Annika Nordin and {\O}yvind Palm and {Van Laar}, {Jacob M.} and Nicolas Hunzelmann and Distler, {J{\"o}rg H W} and Alexander Kreuter and Ariane Herrick and Jane Worthington and Koeleman, {Bobby P.} and Radstake, {Timothy R D J} and Javier Marti{\'n} and Norberto Ortego-Centeno and Raquel R{\'i}os and Nuria Navarrete and Camps, {Mar{\'i}a Teresa} and Antonio Fern{\'a}ndez-Nebro and Gonz{\'a}lez-Escribano, {Mar{\'i}a F.} and Julio S{\'a}nchez-Rom{\'a}n and Castillo, {M. Jes{\'u}s} and {{\'A}ngeles Aguirre}, M. and Benjam{\'i}n Fern{\'a}ndez-Guti{\'e}rrez and Luis Rodr{\'i}guez-Rodr{\'i}guez and Esther Vicente and Andreu, {Jos{\'e} Luis} and {De Castro}, {M{\'o}nica Fern{\'a}ndez} and Lina Mart{\'i}nez and Iv{\'a}n Castellv{\'i} and Anna Pros and Carballeira, {M{\'o}nica Rodr{\'i}guez} and Mej{\'i}as, {Raquel L{\'o}pez} and Bernardino D{\'i}az and Luis Trapiella and Freire, {Mar{\'i}a Del Carmen} and In{\'e}s Vaqueiro and Luis S{\'a}ez-Comet and Federico D{\'i}az and Vanesa Hern{\'a}ndez and Emma Beltr{\'a}n and Robles, {Mar{\'i}a {\'A}ngeles} and Natividad Oreiro",

year = "2012",

month = dec,

doi = "10.3899/jrheum.120506",

language = "English",

volume = "39",

pages = "2294--2302",

journal = "Journal of Rheumatology",

issn = "1499-2752",

publisher = "Journal of Rheumatology",

number = "12",

}

Cénit, MC, Simeón, CP, Vonk, MC, Callejas-Rubio, JL, Espinosa, G, Carreira, P, Blanco, FJ, Narvaez, J, Tolosa, C, Román-Ivorra, JA, Gómez-Garćia, I, García-Hernández, FJ, Gallego, M, García-Portales, R, Egurbide, MV, Fonollosa, V, De La Pẽna, PG, López-Longo, FJ, González-Gay, MA, Hesselstrand, R, Riemekasten, G, Torsten, W, Voskuyl, AE, Schuerwegh, AJ, Madhok, R, Fonseca, C, Denton, C, Nordin, A, Palm, Ø, Van Laar, JM, Hunzelmann, N, Distler, JHW, Kreuter, A, Herrick, A , Worthington, J, Koeleman, BP, Radstake, TRDJ, Martiń, J, Ortego-Centeno, N, Ríos, R, Navarrete, N, Camps, MT, Fernández-Nebro, A, González-Escribano, MF, Sánchez-Román, J, Castillo, MJ, Ángeles Aguirre, M, Fernández-Gutiérrez, B, Rodríguez-Rodríguez, L, Vicente, E, Andreu, JL, De Castro, MF, Martínez, L, Castellví, I, Pros, A, Carballeira, MR, Mejías, RL, Díaz, B, Trapiella, L, Freire, MDC, Vaqueiro, I, Sáez-Comet, L, Díaz, F, Hernández, V, Beltrán, E, Robles, MÁ & Oreiro, N 2012, 'Influence of the IL6 gene in susceptibility to systemic sclerosis', Journal of Rheumatology, vol. 39, no. 12, pp. 2294-2302. https://doi.org/10.3899/jrheum.120506

TY - JOUR

T1 - Influence of the IL6 gene in susceptibility to systemic sclerosis

AU - Cénit, Maria Carmen

AU - Simeón, Carmen P.

AU - Vonk, Madelon C.

AU - Callejas-Rubio, Jose L.

AU - Espinosa, Gerard

AU - Carreira, Patricia

AU - Blanco, Francisco J.

AU - Narvaez, Javier

AU - Tolosa, Carlos

AU - Román-Ivorra, José A.

AU - Gómez-Garćia, Inmaculada

AU - García-Hernández, Francisco J.

AU - Gallego, María

AU - García-Portales, Rosa

AU - Egurbide, María Victoria

AU - Fonollosa, Vicente

AU - De La Pẽna, Paloma García

AU - López-Longo, Francisco J.

AU - González-Gay, Miguel A.

AU - Hesselstrand, Roger

AU - Riemekasten, Gabriela

AU - Torsten, Witte

AU - Voskuyl, Alexandre E.

AU - Schuerwegh, Annemie J.

AU - Madhok, Rajan

AU - Fonseca, Carmen

AU - Denton, Christopher

AU - Nordin, Annika

AU - Palm, Øyvind

AU - Van Laar, Jacob M.

AU - Hunzelmann, Nicolas

AU - Distler, Jörg H W

AU - Kreuter, Alexander

AU - Herrick, Ariane

AU - Worthington, Jane

AU - Koeleman, Bobby P.

AU - Radstake, Timothy R D J

AU - Martiń, Javier

AU - Ortego-Centeno, Norberto

AU - Ríos, Raquel

AU - Navarrete, Nuria

AU - Camps, María Teresa

AU - Fernández-Nebro, Antonio

AU - González-Escribano, María F.

AU - Sánchez-Román, Julio

AU - Castillo, M. Jesús

AU - Ángeles Aguirre, M.

AU - Fernández-Gutiérrez, Benjamín

AU - Rodríguez-Rodríguez, Luis

AU - Vicente, Esther

AU - Andreu, José Luis

AU - De Castro, Mónica Fernández

AU - Martínez, Lina

AU - Castellví, Iván

AU - Pros, Anna

AU - Carballeira, Mónica Rodríguez

AU - Mejías, Raquel López

AU - Díaz, Bernardino

AU - Trapiella, Luis

AU - Freire, María Del Carmen

AU - Vaqueiro, Inés

AU - Sáez-Comet, Luis

AU - Díaz, Federico

AU - Hernández, Vanesa

AU - Beltrán, Emma

AU - Robles, María Ángeles

AU - Oreiro, Natividad

PY - 2012/12

Y1 - 2012/12

N2 - Objective. Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology. Results. Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). Conclusion. Our results suggest that the IL6 gene may influence the development of SSc and its progression. The Journal of Rheumatology Copyright © 2012. All rights reserved.

AB - Objective. Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology. Results. Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). Conclusion. Our results suggest that the IL6 gene may influence the development of SSc and its progression. The Journal of Rheumatology Copyright © 2012. All rights reserved.

KW - Gene

KW - Genetic Studies

KW - IL6

KW - Polymorphisms

KW - Scleroderma

KW - Systemic sclerosis

U2 - 10.3899/jrheum.120506

DO - 10.3899/jrheum.120506

M3 - Article

C2 - 23027890

SN - 1499-2752

VL - 39

SP - 2294

EP - 2302

JO - Journal of Rheumatology

JF - Journal of Rheumatology

IS - 12

ER -

Influence of the IL6 gene in susceptibility to systemic sclerosis

Abstract

Keywords

Access to Document

Fingerprint

Cite this