Brief Report: Association of Genetic Variants in the IL4 and IL4R Genes With the Severity of Joint Damage in Rheumatoid Arthritis: A Study in Seven Cohorts. Issue 12 (December 2013)

• Record Type: Journal Article
• Authors: Krabben, A.; Wilson, A. G.; de Rooy, D. P. C.; Zhernakova, A.; Brouwer, E.; Lindqvist, E.; Saxne, T.; Stoeken, G.; van Nies, J. A. B.; Knevel, R.; Huizinga, T. W. J.; Toes, R.; Gregersen, P. K.; van der Helm‐van Mil, A. H. M.
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 12(2013:Dec.)
• Page Start: 3051
• Page End: 3057
• Publication Date: 2013-12
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.38141
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38141-sec-0001" sec-type="section"> <title>Objective</title> <p>The progression of joint destruction in rheumatoid arthritis (RA) is determined by genetic factors. Changes in <italic>IL4</italic> and <italic>IL4R</italic> genes have been associated with RA severity, but this finding has not been replicated. This study was undertaken to investigate the association between <italic>IL4‐</italic> and <italic>IL4R‐</italic>tagging single‐nucleotide polymorphisms (SNPs) and the progression rate of joint damage in RA in a multicohort candidate gene study.</p> </sec> <sec id="art38141-sec-0002" sec-type="section"> <title>Methods</title> <p> <italic>IL4‐</italic> and <italic>IL4R</italic>‐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.</p> </sec> <sec id="art38141-sec-0003" sec-type="section"> <title>Results</title> <p>In the discovery phase, none of the <italic>IL4</italic> SNPs and 7 of the <italic>IL4R</italic> SNPs were significantly associated with the joint damage progression rate. In the replication phase, 2 SNPs in the <italic>IL4R</italic> gene were significantly associated with the joint damage progression rate (rs1805011 [<italic>P</italic> = 0.02] and rs1119132 [<italic>P</italic> = 0.001]).</p> </sec> <sec id="art38141-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Genetic variants in <italic>IL4R</italic> were identified, and their association with the progression rate of joint damage in RA was independently replicated.</p> </sec> </abstract>