OBJECTIVE: Within the interleukin-1 (IL-1) cytokine family, IL-1 receptor antagonist (IL1RN) gene variants have been associated with radiological severity of knee osteoarthritis (OA) in cross-sectional studies. The present study tested the relation between IL1RN gene variants and progression of knee OA assessed radiographically by change in Kellgren-Lawrence (KL) score over time. DESIGN: 1153 Caucasian adults (age range: 44-89) from the Johnson County Osteoarthritis Project were evaluated for unequivocal radiographic evidence of knee OA at baseline, defined as KL score ≥2, and were re-examined after 4-11 years for radiographic changes typical of OA progression. IL1RN gene variants were tested for association with OA progression and for potential interaction with body mass index (BMI). Other IL-1 gene variations were tested for association with OA progression as a secondary objective. RESULTS: Of 154 subjects with OA at baseline, 88 showed progression at follow-up. Seven IL1RN single nucleotide polymorphisms (SNPs) and one IL-1 receptor SNP were associated with progression. Four IL1RN haplotypes, each occurring in >5% of this population, showed different relationships with progression, including one (rs315931/rs4251961/rs2637988/rs3181052/rs1794066/rs419598/rs380092/rs579543/rs315952/rs9005/rs315943/rs1374281; ACAGATACTGCC) associated with increased progression [odds ratio (OR) 1.91 (95%CI 1.16-3.15); P = 0.012]. Haplotypes associated with progression by KL score were also associated with categorical change in joint space narrowing. BMI was associated with OA progression in subjects carrying a specific IL1RN haplotype, but not in subjects without that haplotype. CONCLUSION: A significantly greater likelihood of radiological progression of knee OA was associated with a commonly occurring IL1RN haplotype that could be tagged by three IL1RN SNPs (rs419598, rs9005, rs315943). Interactions were also observed between IL1RN gene variants and BMI relative to OA progression. This suggests that IL1RN gene markers may be useful in stratifying patients for medical management and drug development.
OBJECTIVE: Within the interleukin-1 (IL-1) cytokine family, IL-1 receptor antagonist (IL1RN) gene variants have been associated with radiological severity of knee osteoarthritis (OA) in cross-sectional studies. The present study tested the relation between IL1RN gene variants and progression of knee OA assessed radiographically by change in Kellgren-Lawrence (KL) score over time. DESIGN: 1153 Caucasian adults (age range: 44-89) from the Johnson County Osteoarthritis Project were evaluated for unequivocal radiographic evidence of knee OA at baseline, defined as KL score ≥2, and were re-examined after 4-11 years for radiographic changes typical of OA progression. IL1RN gene variants were tested for association with OA progression and for potential interaction with body mass index (BMI). Other IL-1 gene variations were tested for association with OA progression as a secondary objective. RESULTS: Of 154 subjects with OA at baseline, 88 showed progression at follow-up. Seven IL1RN single nucleotide polymorphisms (SNPs) and one IL-1 receptor SNP were associated with progression. Four IL1RN haplotypes, each occurring in >5% of this population, showed different relationships with progression, including one (rs315931/rs4251961/rs2637988/rs3181052/rs1794066/rs419598/rs380092/rs579543/rs315952/rs9005/rs315943/rs1374281; ACAGATACTGCC) associated with increased progression [odds ratio (OR) 1.91 (95%CI 1.16-3.15); P = 0.012]. Haplotypes associated with progression by KL score were also associated with categorical change in joint space narrowing. BMI was associated with OA progression in subjects carrying a specific IL1RN haplotype, but not in subjects without that haplotype. CONCLUSION: A significantly greater likelihood of radiological progression of knee OA was associated with a commonly occurring IL1RN haplotype that could be tagged by three IL1RN SNPs (rs419598, rs9005, rs315943). Interactions were also observed between IL1RN gene variants and BMI relative to OA progression. This suggests that IL1RN gene markers may be useful in stratifying patients for medical management and drug development.
Authors: Ingrid Meulenbelt; Josine L Min; Steffan Bos; Naghmeh Riyazi; Jeanine J Houwing-Duistermaat; Henk-Jan van der Wijk; Herman M Kroon; Masahiro Nakajima; Shiro Ikegawa; André G Uitterlinden; Joyce B J van Meurs; Wendy M van der Deure; Theo J Visser; Albert B Seymour; Nico Lakenberg; Ruud van der Breggen; Dennis Kremer; Cornelia M van Duijn; Margreet Kloppenburg; John Loughlin; P Eline Slagboom Journal: Hum Mol Genet Date: 2008-03-11 Impact factor: 6.150
Authors: Hanneke J M Kerkhof; Rik J Lories; Ingrid Meulenbelt; Ingileif Jonsdottir; Ana M Valdes; Pascal Arp; Thorvaldur Ingvarsson; Mila Jhamai; Helgi Jonsson; Lisette Stolk; Gudmar Thorleifsson; Guangju Zhai; Feng Zhang; Yanyan Zhu; Ruud van der Breggen; Andrew Carr; Michael Doherty; Sally Doherty; David T Felson; Antonio Gonzalez; Bjarni V Halldorsson; Deborah J Hart; Valdimar B Hauksson; Albert Hofman; John P A Ioannidis; Margreet Kloppenburg; Nancy E Lane; John Loughlin; Frank P Luyten; Michael C Nevitt; Neeta Parimi; Huibert A P Pols; Fernando Rivadeneira; Eline P Slagboom; Unnur Styrkársdóttir; Aspasia Tsezou; Tom van de Putte; Joseph Zmuda; Tim D Spector; Kari Stefansson; André G Uitterlinden; Joyce B J van Meurs Journal: Arthritis Rheum Date: 2010-02
Authors: Ingrid Meulenbelt; Steffan D Bos; Margreet Kloppenburg; Nico Lakenberg; Jeanine J Houwing-Duistermaat; Iain Watt; Anton J de Craen; Cornelia M van Duijn; P Eline Slagboom Journal: Arthritis Rheum Date: 2010-04
Authors: Alexander P Reiner; Mark M Wurfel; Leslie A Lange; Christopher S Carlson; Alex S Nord; Cara L Carty; Mark J Rieder; Cindy Desmarais; Nancy S Jenny; Carlos Iribarren; Jeremy D Walston; O Dale Williams; Deborah A Nickerson; Gail P Jarvik Journal: Arterioscler Thromb Vasc Biol Date: 2008-05-01 Impact factor: 8.311
Authors: Annu Näkki; Sanna T Kouhia; Janna Saarela; Arsi Harilainen; Kaj Tallroth; Tapio Videman; Michele C Battié; Jaakko Kaprio; Leena Peltonen; Urho M Kujala Journal: BMC Med Genet Date: 2010-03-30 Impact factor: 2.103
Authors: John Rogus; James D Beck; Steven Offenbacher; Kenneth Huttner; Licia Iacoviello; Maria Carmela Latella; Monica de Gaetano; Hwa-Ying Wang; Kenneth S Kornman; Gordon W Duff Journal: Hum Genet Date: 2008-03-28 Impact factor: 4.132
Authors: G Moxley; I Meulenbelt; K Chapman; C M van Diujn; P Eline Slagboom; M C Neale; A J P Smith; A J Carr; J Loughlin Journal: Osteoarthritis Cartilage Date: 2009-09-01 Impact factor: 6.576
Authors: Mukundan Attur; Hwa-Ying Wang; Virginia Byers Kraus; Jack F Bukowski; Nazneen Aziz; Svetlana Krasnokutsky; Jonathan Samuels; Jeffrey Greenberg; Gary McDaniel; Steven B Abramson; Kenneth S Kornman Journal: Ann Rheum Dis Date: 2009-11-23 Impact factor: 19.103
Authors: Shannon L Gillespie; Jeremy L Neal; Lisa M Christian; Laura A Szalacha; Donna O McCarthy; Pamela J Salsberry Journal: Nurs Res Date: 2017 Mar/Apr Impact factor: 2.381
Authors: Mukundan Attur; Svetlana Krasnokutsky; Alexander Statnikov; Jonathan Samuels; Zhiguo Li; Olga Friese; Marie-Pierre Hellio Le Graverand-Gastineau; Leon Rybak; Virginia B Kraus; Joanne M Jordan; Constantin F Aliferis; Steven B Abramson Journal: Arthritis Rheumatol Date: 2015-11 Impact factor: 10.995
Authors: Eziamaka C Okafor; Gangadhar M Utturkar; Margaret R Widmyer; Ermias S Abebe; Amber T Collins; Dean C Taylor; Charles E Spritzer; C T Moorman; William E Garrett; Louis E DeFrate Journal: J Biomech Date: 2013-10-19 Impact factor: 2.712
Authors: M Attur; A Statnikov; J Samuels; Z Li; A V Alekseyenko; J D Greenberg; S Krasnokutsky; L Rybak; Q A Lu; J Todd; H Zhou; J M Jordan; V B Kraus; C F Aliferis; S B Abramson Journal: Osteoarthritis Cartilage Date: 2015-11 Impact factor: 6.576