OBJECTIVE: The progression of joint destruction in rheumatoid arthritis (RA) is determined by genetic factors. Changes in IL4 and IL4R genes have been associated with RA severity, but this finding has not been replicated. This study was undertaken to investigate the association between IL4- and IL4R-tagging single-nucleotide polymorphisms (SNPs) and the progression rate of joint damage in RA in a multicohort candidate gene study. METHODS: IL4- and IL4R-tagging SNPs (n = 8 and 39, respectively) were genotyped in 600 RA patients for whom 2,846 sets of radiographs of the hands and feet were obtained during 7 years of followup. Subsequently, SNPs significantly associated with the progression of joint damage were genotyped and studied in relation to 3,415 radiographs of 1,953 RA patients; these included data sets from Groningen (The Netherlands), Lund (Sweden), Sheffield (UK), the North American Rheumatoid Arthritis Consortium (US), Wichita (US), and the National Data Bank (US). The relative increase in progression rate per year in the presence of a genotype was determined in each cohort. An inverse variance weighting meta-analysis was performed on the 6 data sets that together formed the replication phase. RESULTS: In the discovery phase, none of the IL4 SNPs and 7 of the IL4R SNPs were significantly associated with the joint damage progression rate. In the replication phase, 2 SNPs in the IL4R gene were significantly associated with the joint damage progression rate (rs1805011 [P = 0.02] and rs1119132 [P = 0.001]). CONCLUSION: Genetic variants in IL4R were identified, and their association with the progression rate of joint damage in RA was independently replicated.
OBJECTIVE: The progression of joint destruction in rheumatoid arthritis (RA) is determined by genetic factors. Changes in IL4 and IL4R genes have been associated with RA severity, but this finding has not been replicated. This study was undertaken to investigate the association between IL4- and IL4R-tagging single-nucleotide polymorphisms (SNPs) and the progression rate of joint damage in RA in a multicohort candidate gene study. METHODS:IL4- and IL4R-tagging SNPs (n = 8 and 39, respectively) were genotyped in 600 RApatients for whom 2,846 sets of radiographs of the hands and feet were obtained during 7 years of followup. Subsequently, SNPs significantly associated with the progression of joint damage were genotyped and studied in relation to 3,415 radiographs of 1,953 RApatients; these included data sets from Groningen (The Netherlands), Lund (Sweden), Sheffield (UK), the North American Rheumatoid Arthritis Consortium (US), Wichita (US), and the National Data Bank (US). The relative increase in progression rate per year in the presence of a genotype was determined in each cohort. An inverse variance weighting meta-analysis was performed on the 6 data sets that together formed the replication phase. RESULTS: In the discovery phase, none of the IL4 SNPs and 7 of the IL4R SNPs were significantly associated with the joint damage progression rate. In the replication phase, 2 SNPs in the IL4R gene were significantly associated with the joint damage progression rate (rs1805011 [P = 0.02] and rs1119132 [P = 0.001]). CONCLUSION: Genetic variants in IL4R were identified, and their association with the progression rate of joint damage in RA was independently replicated.
Authors: Munitta Muthana; Sarah Hawtree; Adam Wilshaw; Eimear Linehan; Hannah Roberts; Sachin Khetan; Gbadebo Adeleke; Fiona Wright; Mohammed Akil; Ursula Fearon; Douglas Veale; Barbara Ciani; Anthony G Wilson Journal: Proc Natl Acad Sci U S A Date: 2015-08-27 Impact factor: 11.205
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Authors: Hanna W van Steenbergen; Luis Rodríguez-Rodríguez; Ewa Berglin; Alexandra Zhernakova; Rachel Knevel; Jose Ivorra-Cortés; Tom W J Huizinga; Benjamin Fernández-Gutiérrez; Peter K Gregersen; Solbritt Rantapää-Dahlqvist; Annette H M van der Helm-van Mil Journal: Arthritis Res Ther Date: 2015-01-08 Impact factor: 5.156
Authors: G Anovazzi; M C Medeiros; S C Pigossi; L S Finoti; T M Souza Moreira; M P A Mayer; C F Zanelli; S R Valentini; C Rossa-Junior; R M Scarel-Caminaga Journal: Genes Immun Date: 2017-01-05 Impact factor: 2.676
Authors: Xiang Li; Wei Chai; Ming Ni; Meng Xu; Zijian Lian; Lewis Shi; Yang Bai; Yan Wang Journal: Biomed Res Int Date: 2014-02-23 Impact factor: 3.411
Authors: Sebastien Viatte; James C Lee; Bo Fu; Marion Espéli; Mark Lunt; Jack N E De Wolf; Lily Wheeler; John A Reynolds; Madhura Castelino; Deborah P M Symmons; Paul A Lyons; Anne Barton; Kenneth G C Smith Journal: Arthritis Rheumatol Date: 2016-11 Impact factor: 10.995