OBJECTIVE: It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well-powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA. METHODS: Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single-nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case-control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects. RESULTS: No fully significant associations were observed. Analysis of the discovery case-control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case-control samples. No association with rheumatoid factor, anti-cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here. CONCLUSION: In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA.
OBJECTIVE: It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well-powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA. METHODS: Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single-nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case-control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects. RESULTS: No fully significant associations were observed. Analysis of the discovery case-control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case-control samples. No association with rheumatoid factor, anti-cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here. CONCLUSION: In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA.
Authors: P Barrera; S Fauré; J F Prud'homme; A Balsa; P Migliorini; D Chimenti; T R Radstake; L B van de Putte; D Pascual-Salcedo; R Westhovens; K Maenaut; H Alves; A Lopes-Vaz; C Stravopoulos; M Spyropoulou; P Fritz; T Bardin; D Charron; V Lepage; M Martinez; F Cornélis Journal: Clin Exp Rheumatol Date: 2001 Nov-Dec Impact factor: 4.473
Authors: Stacey B Gabriel; Stephen F Schaffner; Huy Nguyen; Jamie M Moore; Jessica Roy; Brendan Blumenstiel; John Higgins; Matthew DeFelice; Amy Lochner; Maura Faggart; Shau Neen Liu-Cordero; Charles Rotimi; Adebowale Adeyemo; Richard Cooper; Ryk Ward; Eric S Lander; Mark J Daly; David Altshuler Journal: Science Date: 2002-05-23 Impact factor: 47.728
Authors: Robert M Plenge; Chris Cotsapas; Leela Davies; Alkes L Price; Paul I W de Bakker; Julian Maller; Itsik Pe'er; Noel P Burtt; Brendan Blumenstiel; Matt DeFelice; Melissa Parkin; Rachel Barry; Wendy Winslow; Claire Healy; Robert R Graham; Benjamin M Neale; Elena Izmailova; Ronenn Roubenoff; Alexander N Parker; Roberta Glass; Elizabeth W Karlson; Nancy Maher; David A Hafler; David M Lee; Michael F Seldin; Elaine F Remmers; Annette T Lee; Leonid Padyukov; Lars Alfredsson; Jonathan Coblyn; Michael E Weinblatt; Stacey B Gabriel; Shaun Purcell; Lars Klareskog; Peter K Gregersen; Nancy A Shadick; Mark J Daly; David Altshuler Journal: Nat Genet Date: 2007-11-04 Impact factor: 38.330
Authors: Damini Jawaheer; Michael F Seldin; Christopher I Amos; Wei V Chen; Russell Shigeta; Carol Etzel; Aarti Damle; Xiangli Xiao; Dong Chen; Raymond F Lum; Joanita Monteiro; Marlene Kern; Lindsey A Criswell; Salvatore Albani; J Lee Nelson; Daniel O Clegg; Richard Pope; Harry W Schroeder; S Louis Bridges; David S Pisetsky; Ryk Ward; Daniel L Kastner; Ronald L Wilder; Theodore Pincus; Leigh F Callahan; Donald Flemming; Mark H Wener; Peter K Gregersen Journal: Arthritis Rheum Date: 2003-04
Authors: James F Fries; Frederick Wolfe; Raymond Apple; Henry Erlich; Teodorica Bugawan; Tyson Holmes; Bonnie Bruce Journal: Arthritis Rheum Date: 2002-09
Authors: Stéphane Genevay; Francesco S Di Giovine; Thomas V Perneger; Tania Silvestri; Sibylle Stingelin; Gordon Duff; Pierre-André Guerne Journal: Arthritis Rheum Date: 2002-06-15
Authors: C Albuquerque; F Morinha; J Magalhães; J Requicha; I Dias; H Guedes-Pinto; E Bastos; C Viegas Journal: J Genet Date: 2015-12 Impact factor: 1.166