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251. Correction: Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy.

Author

Olga Gorlova, Jose-Ezequiel Martin, Blanca Rueda, Bobby P. C. Koeleman, Jun Ying, Maria Teruel, Lina-Marcela Diaz-Gallo, Jasper C. Broen, Madelon C. Vonk, Carmen P. Simeon, Behrooz Z. Alizadeh, Marieke J. H. Coenen, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Piet L. C. M. van Riel, Marie Vanthuyne, Ruben van 't Slot, Annet Italiaander, Roel A. Ophoff, Nicolas Hunzelmann, Vicente Fonollosa, Norberto Ortego-Centeno, Miguel A. González-Gay, Francisco J. García-Hernández, María F. González-Escribano, Paolo Airo, Jacob van Laar, Jane Worthington, Roger Hesselstrand, Vanessa Smith, Filip de Keyser, Fredric Houssiau, Meng May Chee, Rajan Madhok, Paul G. Shiels, Rene Westhovens, Alexander Kreuter, Elfride de Baere, Torsten Witte, Leonid Padyukov, Annika Nordin, Raffaella Scorza, Claudio Lunardi, Benedicte A. Lie, Anna-Maria Hoffmann-Vold, Øyvind Palm, Paloma García de la Peña, Patricia Carreira, John Varga, Monique Hinchcliff, Annette T. Lee, Pravitt Gourh, Christopher I. Amos, Frederick M. Wigley, Laura K. Hummers, J. Lee Nelson, Gabriella Riemekasten, Ariane Herrick, Lorenzo Beretta, Carmen Fonseca, Christopher P. Denton, Peter K. Gregersen, Sandeep Agarwal, Shervin Assassi, Filemon K. Tan, Frank C. Arnett, Timothy R. D. J. Radstake, Maureen D. Mayes, and Javier Martin

Subjects
Genetics, QH426-470
Published
2011
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252. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.

Author

Yannick Allanore, Mohamad Saad, Philippe Dieudé, Jérôme Avouac, Jorg H W Distler, Philippe Amouyel, Marco Matucci-Cerinic, Gabriella Riemekasten, Paolo Airo, Inga Melchers, Eric Hachulla, Daniele Cusi, H-Erich Wichmann, Julien Wipff, Jean-Charles Lambert, Nicolas Hunzelmann, Kiet Tiev, Paola Caramaschi, Elisabeth Diot, Otylia Kowal-Bielecka, Gabriele Valentini, Luc Mouthon, László Czirják, Nemanja Damjanov, Erika Salvi, Costanza Conti, Martina Müller, Ulf Müller-Ladner, Valeria Riccieri, Barbara Ruiz, Jean-Luc Cracowski, Luc Letenneur, Anne Marie Dupuy, Oliver Meyer, André Kahan, Arnold Munnich, Catherine Boileau, and Maria Martinez

Subjects
Genetics, QH426-470
Abstract

Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P

Published
2011
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253. Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

Author

Olga Gorlova, Jose-Ezequiel Martin, Blanca Rueda, Bobby P C Koeleman, Jun Ying, Maria Teruel, Lina-Marcela Diaz-Gallo, Jasper C Broen, Madelon C Vonk, Carmen P Simeon, Behrooz Z Alizadeh, Marieke J H Coenen, Alexandre E Voskuyl, Annemie J Schuerwegh, Piet L C M van Riel, Marie Vanthuyne, Ruben van 't Slot, Annet Italiaander, Roel A Ophoff, Nicolas Hunzelmann, Vicente Fonollosa, Norberto Ortego-Centeno, Miguel A González-Gay, Francisco J García-Hernández, María F González-Escribano, Paolo Airo, Jacob van Laar, Jane Worthington, Roger Hesselstrand, Vanessa Smith, Filip de Keyser, Fredric Houssiau, Meng May Chee, Rajan Madhok, Paul G Shiels, Rene Westhovens, Alexander Kreuter, Elfride de Baere, Torsten Witte, Leonid Padyukov, Annika Nordin, Raffaella Scorza, Claudio Lunardi, Benedicte A Lie, Anna-Maria Hoffmann-Vold, Oyvind Palm, Paloma García de la Peña, Patricia Carreira, Spanish Scleroderma Group, John Varga, Monique Hinchcliff, Annette T Lee, Pravitt Gourh, Christopher I Amos, Frederick M Wigley, Laura K Hummers, J Lee Nelson, Gabriella Riemekasten, Ariane Herrick, Lorenzo Beretta, Carmen Fonseca, Christopher P Denton, Peter K Gregersen, Sandeep Agarwal, Shervin Assassi, Filemon K Tan, Frank C Arnett, Timothy R D J Radstake, Maureen D Mayes, and Javier Martin

Subjects
Genetics, QH426-470
Abstract

The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84×10(-21), OR = 0.55) and ATA (P = 1.14×10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.

Published
2011
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254. Sex influence on outcomes of patients with systemic sclerosis-associated interstitial lung disease: an EUSTAR database analysis

Author

Campochiaro, Corrado, Hoffmann-Vold, Anna-Maria, Avouac, Jerome, Henes, Jörg, de Vries-Bouwstra, Jeska, Smith, Vanessa, Siegert, Elise, Airò, Paolo, Oksel, Fahrettin, Pellerito, Raffaele, Vanthuyne, Marie, Pozzi, Maria Rosa, Inanc, Murat, Sibilia, Jean, Gabrielli, Armando, Distler, Oliver, Allanore Yannick, EUSTAR Group Marco Matucci Cerinic, Ulrich Walker, Florenzo Iannone, Radim Becvar, Giovanna Cuomo, C Montecucco, Patricia E Carreira, Michele Iudici, Eugene J Kucharz, Elisabetta Zanatta, Pr Dominique Farge Bancel, Roger Hesselstrand, Alexandra Balbir-Gurman, Raffaele Pellerito, Eugenia Bertoldo, Nemanja Damjanov, Vera Ortiz-Santamaria Granollers, Stefan Heitmann, Maria João Salvador, Bojana Stamenkovic, Carlo Francesco Selmi, Ariane Herrick, Ulf Müller-Ladner, Merete Engelhart, Valeria Riccieri, Ruxandra Maria Ionescu, Ana Maria Gheorghiu, Cord Sunderkӧtter, Joӧrg Distler, Francesca Ingegnoli, Luc Mouthon, Corrado, Campochiaro, Anna-Maria, Hoffmann-Vold, Jerome, Avouac, Jörg, Hene, Jeska, de Vries-Bouwstra, Vanessa, Smith, Elise, Siegert, Paolo, Airò, Fahrettin, Oksel, Raffaele, Pellerito, Marie, Vanthuyne, Maria Rosa, Pozzi, Murat, Inanc, Jean, Sibilia, Armando, Gabrielli, Oliver, Distler, Yannick, Allanore, Group Marco Matucci Cerinic, Eustar, Walker, Ulrich, Iannone, Florenzo, Becvar, Radim, Cuomo, Giovanna, Montecucco, C, E Carreira, Patricia, Iudici, Michele, J Kucharz, Eugene, Zanatta, Elisabetta, Dominique Farge Bancel, Pr, Hesselstrand, Roger, Balbir-Gurman, Alexandra, Pellerito, Raffaele, Bertoldo, Eugenia, Damjanov, Nemanja, Ortiz-Santamaria Granollers, Vera, Heitmann, Stefan, João Salvador, Maria, Stamenkovic, Bojana, Francesco Selmi, Carlo, Herrick, Ariane, Müller-Ladner, Ulf, Engelhart, Merete, Riccieri, Valeria, Maria Ionescu, Ruxandra, Maria Gheorghiu, Ana, Sunderkӧtter, Cord, Distler, Joӧrg, Ingegnoli, Francesca, and Mouthon, Luc

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Objective Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc) patients. We aimed to investigate the impact of sex on SSc-ILD. Methods EUSTAR SSc patients with radiologically confirmed ILD and available percentage predicted forced vital capacity (%pFVC) were included. Demographics and disease features were recorded. A change in %pFVC over 12 months (s.d. 6) (cohort 1) was classified into stable (≤4%), mild (5–9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), the %pFVC change at each 12-month (s.d. 6) interval was calculated. Logistic regression analyses [odds ratio (OR) and 95% CI] and Cox proportional hazards models adjusted for age and %pFVC were applied. Results A total of 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, had a higher prevalence of CRP elevation and frequently had diffuse cutaneous involvement. In cohort 1 (1655 females and 390 males), a higher percentage of males had stable ILD (74.4% vs 69.4%, P = 0.056). In multivariable analysis, disease duration and %pFVC [OR 0.99 (95% CI 0.98, 0.99) and OR 0.97 (95% CI 0.95, 0.99), respectively] in males and age, %pFVC and anti-centromere [OR 1.02 (95% CI 1.00, 1.04), OR 0.97 (95% CI 0.96, 0.98) and OR 0.39 (95% CI 0.245, 0.63), respectively] in females were associated with large progression. The 1-year mortality rate was higher in males (5.1% vs 2.5%, P = 0.013). In cohort 2 (849 females and 209 males), a higher percentage of females showed periods of large progression (11.7% vs 7.7%, P = 0.023), the percentage of patients with none, one or two periods of worsening was not different. The overall death rate was 30.9% for males and 20.4% in females (P Conclusions Male SSc-ILD patients have a poorer prognosis and sex-specific predictors exist in SSc-ILD.

Published
2022

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