OBJECTIVE: Independent replication with large cohorts and metaanalysis of genetic associations are necessary to validate genetic susceptibility factors. The known tumor necrosis factor (ligand) superfamily, member 4 gene (TNFSF4) systemic lupus erythematosus (SLE) risk locus has been found to be associated with systemic sclerosis (SSc) in 2 studies, but with discrepancies between them for genotype-phenotype correlation. Our objective was to validate TNFSF4 association with SSc and determine the subset with the higher risk. METHODS: Known SLE and SSc TNFSF4 susceptibility variants (rs2205960, rs1234317, rs12039904, rs10912580, and rs844648) were genotyped in 1031 patients with SSc and 1014 controls of French white ancestry. Genotype-phenotype association analysis and meta analysis of available data were performed, providing a population study of 4989 patients with SSc and 4661 controls, all of European white ancestry. RESULTS: Allelic and genotypic associations were observed for the 5 single-nucleotide polymorphisms (SNP) with the subset of patients with SSc who are positive for anticentromere antibodies (ACA) and only a trend for association with SSc and limited cutaneous SSc. Rs2205960 exhibited the strongest allelic association in ACA+ patients with SSc [p = 0.0015; OR 1.37 (1.12-1.66)], with significant intra-cohort association when compared to patients with SSc positive for ACA. Metaanalysis confirmed overall association with SSc but also raised preferential association with the ACA+ subset and strongest effect with rs2205960 [T allele p = 0.00013; OR 1.33 (1.15-1.54) and TT genotype p = 0.00046; OR 2.02 (1.36-2.98)]. CONCLUSION: We confirm TNFSF4 as an SSc susceptibility gene and rs2205960 as a putative causal variant with preferential association in the ACA+ SSc subphenotype.
OBJECTIVE: Independent replication with large cohorts and metaanalysis of genetic associations are necessary to validate genetic susceptibility factors. The known tumor necrosis factor (ligand) superfamily, member 4 gene (TNFSF4) systemic lupus erythematosus (SLE) risk locus has been found to be associated with systemic sclerosis (SSc) in 2 studies, but with discrepancies between them for genotype-phenotype correlation. Our objective was to validate TNFSF4 association with SSc and determine the subset with the higher risk. METHODS: Known SLE and SSc TNFSF4 susceptibility variants (rs2205960, rs1234317, rs12039904, rs10912580, and rs844648) were genotyped in 1031 patients with SSc and 1014 controls of French white ancestry. Genotype-phenotype association analysis and meta analysis of available data were performed, providing a population study of 4989 patients with SSc and 4661 controls, all of European white ancestry. RESULTS: Allelic and genotypic associations were observed for the 5 single-nucleotide polymorphisms (SNP) with the subset of patients with SSc who are positive for anticentromere antibodies (ACA) and only a trend for association with SSc and limited cutaneous SSc. Rs2205960 exhibited the strongest allelic association in ACA+ patients with SSc [p = 0.0015; OR 1.37 (1.12-1.66)], with significant intra-cohort association when compared to patients with SSc positive for ACA. Metaanalysis confirmed overall association with SSc but also raised preferential association with the ACA+ subset and strongest effect with rs2205960 [T allele p = 0.00013; OR 1.33 (1.15-1.54) and TT genotype p = 0.00046; OR 2.02 (1.36-2.98)]. CONCLUSION: We confirm TNFSF4 as an SSc susceptibility gene and rs2205960 as a putative causal variant with preferential association in the ACA+ SSc subphenotype.
Authors: G Nordmark; G Kristjansdottir; E Theander; S Appel; P Eriksson; L Vasaitis; M Kvarnström; N Delaleu; P Lundmark; A Lundmark; C Sjöwall; J G Brun; M V Jonsson; E Harboe; L G Gøransson; S J Johnsen; P Söderkvist; M-L Eloranta; G Alm; E Baecklund; M Wahren-Herlenius; R Omdal; L Rönnblom; R Jonsson; A-C Syvänen Journal: Genes Immun Date: 2010-09-23 Impact factor: 2.676
Authors: Lara Bossini-Castillo; Jasper C A Broen; Carmen P Simeon; Lorenzo Beretta; Madelon C Vonk; Norberto Ortego-Centeno; Gerard Espinosa; Patricia Carreira; María Teresa Camps; Nuria Navarrete; María F González-Escribano; Esther Vicente-Rabaneda; Luis Rodríguez; Carlos Tolosa; José A Román-Ivorra; Inmaculada Gómez-Gracia; Francisco J García-Hernández; Iván Castellví; María Gallego; Antonio Fernández-Nebro; Rosa García-Portales; María Victoria Egurbide; Vicente Fonollosa; Paloma García de la Peña; Ana Pros; Miguel A González-Gay; Roger Hesselstrand; Gabriela Riemekasten; Torsten Witte; Marieke J H Coenen; Bobby P Koeleman; Frederic Houssiau; Vanessa Smith; Filip de Keyser; Rene Westhovens; Ellen De Langhe; Alexandre E Voskuyl; Annemie J Schuerwegh; Meng May Chee; Rajan Madhok; Paul Shiels; Carmen Fonseca; Christopher Denton; Kathleen Claes; Leonid Padykov; Annika Nordin; Oyvind Palm; Benedicte A Lie; Paolo Airó; Raffaella Scorza; Jacob M van Laar; Nicolas Hunzelmann; Alexander Kreuter; Ariane Herrick; Jane Worthington; Timothy R D J Radstake; Javier Martín; Blanca Rueda Journal: Ann Rheum Dis Date: 2010-12-27 Impact factor: 19.103
Authors: S Klein; C C Kretz; V Ruland; C Stumpf; M Haust; W Hartschuh; M Hartmann; A Enk; E Suri-Payer; N Oberle; P H Krammer; A Kuhn Journal: Ann Rheum Dis Date: 2010-11-19 Impact factor: 19.103
Authors: L M Diaz-Gallo; P Gourh; J Broen; C Simeon; V Fonollosa; N Ortego-Centeno; S Agarwal; M C Vonk; M Coenen; G Riemekasten; N Hunzelmann; R Hesselstrand; F K Tan; J D Reveille; S Assassi; F J García-Hernandez; P Carreira; M T Camps; A Fernandez-Nebro; P Garcia de la Peña; T Nearney; D Hilda; M A González-Gay; P Airo; L Beretta; R Scorza; A Herrick; J Worthington; A Pros; I Gómez-Gracia; L Trapiella; G Espinosa; I Castellvi; T Witte; F de Keyser; M Vanthuyne; M D Mayes; T R D J Radstake; F C Arnett; J Martin; B Rueda Journal: Ann Rheum Dis Date: 2010-12-03 Impact factor: 19.103
Authors: 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; 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; Javier Martin Journal: PLoS Genet Date: 2011-07-14 Impact factor: 5.917
Authors: Pravitt Gourh; Frank C Arnett; Filemon K Tan; Shervin Assassi; Dipal Divecha; Gene Paz; Terry McNearney; Hilda Draeger; John D Reveille; Maureen D Mayes; Sandeep K Agarwal Journal: Ann Rheum Dis Date: 2009-09-23 Impact factor: 19.103
Authors: Debendra Pattanaik; Monica Brown; Bradley C Postlethwaite; Arnold E Postlethwaite Journal: Front Immunol Date: 2015-06-08 Impact factor: 7.561
Authors: Jonathan Sitrin; Eric Suto; Arthur Wuster; Jeffrey Eastham-Anderson; Jeong M Kim; Cary D Austin; Wyne P Lee; Timothy W Behrens Journal: J Immunol Date: 2017-07-10 Impact factor: 5.422
Authors: Yoshihiro Inamoto; Paul J Martin; Mary E D Flowers; Stephanie J Lee; Paul A Carpenter; Edus H Warren; Daniel E Geraghty; Ni Lee; Michael J Boeckh; Barry E Storer; David M Levine; Wenhong Fan; Lue-Ping Zhao; John A Hansen Journal: Blood Date: 2016-06-16 Impact factor: 22.113