Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis

C. McKinney; J. C.A. Broen; M. C. Vonk; L. Beretta; R. Hesselstrand; N. Hunzelmann; G. Riemekasten; R. Scorza; C. P. Simeon; V. Fonollosa; P. E. Carreira; N. Ortego-Centeno; M. A. Gonzalez-Gay; P. Airo; M. Coenen; J. Martin; T. R.D.J. Radstake; T. R. Merriman

doi:10.1038/gene.2012.15

Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis

C. McKinney, J. C.A. Broen, M. C. Vonk, L. Beretta, R. Hesselstrand, N. Hunzelmann, G. Riemekasten, R. Scorza, C. P. Simeon, V. Fonollosa, P. E. Carreira, N. Ortego-Centeno, M. A. Gonzalez-Gay, P. Airo, M. Coenen, J. Martin, T. R.D.J. Radstake, T. R. Merriman^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Klinik für Rheumatologie und klinische Immunologie

30 Zitate (Scopus)

Abstract

There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN≥2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.

Originalsprache	Englisch
Zeitschrift	Genes and Immunity
Jahrgang	13
Ausgabenummer	6
Seiten (von - bis)	458-460
Seitenumfang	3
ISSN	1466-4879
DOIs	https://doi.org/10.1038/gene.2012.15
Publikationsstatus	Veröffentlicht - 09.2012

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The Health Research Council of NZ and NZ Lottery Health are thanked for financial support. JM was funded by grant SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain, by Redes Temáticas de Investigación Cooperativa Sanitaria Programme, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain, and by Fondo Europeo de Desarrollo Regional (FEDER).

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10.1038/gene.2012.15

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McKinney, C., Broen, J. C. A., Vonk, M. C., Beretta, L., Hesselstrand, R., Hunzelmann, N., Riemekasten, G., Scorza, R., Simeon, C. P., Fonollosa, V., Carreira, P. E., Ortego-Centeno, N., Gonzalez-Gay, M. A., Airo, P., Coenen, M., Martin, J., Radstake, T. R. D. J., & Merriman, T. R. (2012). Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis. Genes and Immunity, 13(6), 458-460. https://doi.org/10.1038/gene.2012.15

@article{f1170114386d45ca881fb7921ce44763,

title = "Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis",

abstract = "There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN≥2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.",

author = "C. McKinney and Broen, \{J. C.A.\} and Vonk, \{M. C.\} and L. Beretta and R. Hesselstrand and N. Hunzelmann and G. Riemekasten and R. Scorza and Simeon, \{C. P.\} and V. Fonollosa and Carreira, \{P. E.\} and N. Ortego-Centeno and Gonzalez-Gay, \{M. A.\} and P. Airo and M. Coenen and J. Martin and Radstake, \{T. R.D.J.\} and Merriman, \{T. R.\}",

note = "Funding Information: The Health Research Council of NZ and NZ Lottery Health are thanked for financial support. JM was funded by grant SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andaluc{\'i}a, Spain, by Redes Tem{\'a}ticas de Investigaci{\'o}n Cooperativa Sanitaria Programme, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain, and by Fondo Europeo de Desarrollo Regional (FEDER). Copyright: Copyright 2013 Elsevier B.V., All rights reserved.",

year = "2012",

month = sep,

doi = "10.1038/gene.2012.15",

language = "English",

volume = "13",

pages = "458--460",

journal = "Genes and Immunity",

issn = "1466-4879",

publisher = "Springer Nature",

number = "6",

}

McKinney, C, Broen, JCA, Vonk, MC, Beretta, L, Hesselstrand, R, Hunzelmann, N, Riemekasten, G, Scorza, R, Simeon, CP, Fonollosa, V, Carreira, PE, Ortego-Centeno, N, Gonzalez-Gay, MA, Airo, P, Coenen, M, Martin, J, Radstake, TRDJ & Merriman, TR 2012, 'Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis', Genes and Immunity, Jg. 13, Nr. 6, S. 458-460. https://doi.org/10.1038/gene.2012.15

TY - JOUR

T1 - Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis

AU - McKinney, C.

AU - Broen, J. C.A.

AU - Vonk, M. C.

AU - Beretta, L.

AU - Hesselstrand, R.

AU - Hunzelmann, N.

AU - Riemekasten, G.

AU - Scorza, R.

AU - Simeon, C. P.

AU - Fonollosa, V.

AU - Carreira, P. E.

AU - Ortego-Centeno, N.

AU - Gonzalez-Gay, M. A.

AU - Airo, P.

AU - Coenen, M.

AU - Martin, J.

AU - Radstake, T. R.D.J.

AU - Merriman, T. R.

N1 - Funding Information: The Health Research Council of NZ and NZ Lottery Health are thanked for financial support. JM was funded by grant SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain, by Redes Temáticas de Investigación Cooperativa Sanitaria Programme, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain, and by Fondo Europeo de Desarrollo Regional (FEDER). Copyright: Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2012/9

Y1 - 2012/9

N2 - There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN≥2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.

AB - There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN≥2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.

UR - https://www.scopus.com/pages/publications/84865645411

U2 - 10.1038/gene.2012.15

DO - 10.1038/gene.2012.15

M3 - Journal articles

C2 - 22551723

AN - SCOPUS:84865645411

SN - 1466-4879

VL - 13

SP - 458

EP - 460

JO - Genes and Immunity

JF - Genes and Immunity

IS - 6

ER -

Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis

Abstract

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