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Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study

Bossini-Castillo, Lara; Ezequiel Martin, Jose; Broen, Jasper; Simeon, Carmen P.; Beretta, Lorenzo; Gorlova, Olga Y.; Vonk, Madelon C.; Ortego-Centeno, Norberto; Espinosa, Gerard and Carreira, Patricia, et al. (2013) In Annals of the Rheumatic Diseases 72(4). p.602-607
Abstract
Introduction A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. Methods 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression... (More)
Introduction A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. Methods 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. Results Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 p(MH) = 1.94 x 10(-4), OR 1.19; rs4958881 p(MH) = 3.26 x 10(-5), OR 1.19; rs3792783 p(MH) = 2.16 x 10(-4), OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. Conclusions These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor. (Less)
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Annals of the Rheumatic Diseases
volume
72
issue
4
pages
602 - 607
publisher
British Medical Association
external identifiers
  • wos:000315378500022
  • scopus:84874399330
ISSN
1468-2060
DOI
10.1136/annrheumdis-2012-201888
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English
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yes
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9d56e6be-a3c9-4f7f-89c7-01422db0fe8f (old id 3669874)
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@article{9d56e6be-a3c9-4f7f-89c7-01422db0fe8f,
  abstract     = {Introduction A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. Methods 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. Results Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 p(MH) = 1.94 x 10(-4), OR 1.19; rs4958881 p(MH) = 3.26 x 10(-5), OR 1.19; rs3792783 p(MH) = 2.16 x 10(-4), OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. Conclusions These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor.},
  author       = {Bossini-Castillo, Lara and Ezequiel Martin, Jose and Broen, Jasper and Simeon, Carmen P. and Beretta, Lorenzo and Gorlova, Olga Y. and Vonk, Madelon C. and Ortego-Centeno, Norberto and Espinosa, Gerard and Carreira, Patricia and Garcia de la Pena, Paloma and Oreiro, Natividad and Andres Roman-Ivorra, Jose and Jesus Castillo, Maria and Gonzalez-Gay, Miguel A. and Saez-Comet, Luis and Castellvi, Ivan and Schuerwegh, Annemie J. and Voskuyl, Alexandre E. and Hoffmann-Vold, Anna-Maria and Hesselstrand, Roger and Nordin, Annika and Lunardi, Claudio and Scorza, Raffaella and van Laar, Jacob M. and Shiels, Paul G. and Herrick, Ariane and Worthington, Jane and Fonseca, Carmen and Denton, Christopher and Tan, Filemon K. and Arnett, Frank C. and Assassi, Shervin and Koeleman, Bobby P. and Mayes, Maureen D. and Radstake, Timothy R. D. J. and Martin, Javier},
  issn         = {1468-2060},
  language     = {eng},
  number       = {4},
  pages        = {602--607},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study},
  url          = {http://dx.doi.org/10.1136/annrheumdis-2012-201888},
  volume       = {72},
  year         = {2013},
}