OBJECTIVE: To study the role of the interleukin-1 beta gene (IL1B) and the IL-1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine. METHODS: The study population consisted of a random sample of 886 subjects (ages 55-65 years) from a population-based cohort (the Rotterdam study). Two polymorphisms within IL1B (3953C>T and -511C>T) and one within IL1RN (the variable-number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA. Haplotyping and simultaneous logistic regression analysis were performed to investigate whether the associations observed were independent. RESULTS: Associations with a predisposition for hip ROA were observed for heterozygous and homozygous carriers of the rare IL1B allele -511T (crude odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.0-3.4 and OR 2.9, 95% CI 1.4-6.3, respectively) and of the IL1RN VNTR allele 2 (crude OR 2.0, 95% CI 1.1-3.4 and OR 3.3, 95% CI 1.4-7.8, respectively). An additive effect was observed for carriers of risk alleles of both polymorphisms, with a significant linear-by-linear association (P = 0.00022). CONCLUSION: Our findings suggest that the IL-1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.
OBJECTIVE: To study the role of the interleukin-1 beta gene (IL1B) and the IL-1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine. METHODS: The study population consisted of a random sample of 886 subjects (ages 55-65 years) from a population-based cohort (the Rotterdam study). Two polymorphisms within IL1B (3953C>T and -511C>T) and one within IL1RN (the variable-number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA. Haplotyping and simultaneous logistic regression analysis were performed to investigate whether the associations observed were independent. RESULTS: Associations with a predisposition for hip ROA were observed for heterozygous and homozygous carriers of the rare IL1B allele -511T (crude odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.0-3.4 and OR 2.9, 95% CI 1.4-6.3, respectively) and of the IL1RN VNTR allele 2 (crude OR 2.0, 95% CI 1.1-3.4 and OR 3.3, 95% CI 1.4-7.8, respectively). An additive effect was observed for carriers of risk alleles of both polymorphisms, with a significant linear-by-linear association (P = 0.00022). CONCLUSION: Our findings suggest that the IL-1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.
Authors: Ivona Aksentijevich; Seth L Masters; Polly J Ferguson; Paul Dancey; Joost Frenkel; Annet van Royen-Kerkhoff; Ron Laxer; Ulf Tedgård; Edward W Cowen; Tuyet-Hang Pham; Matthew Booty; Jacob D Estes; Netanya G Sandler; Nicole Plass; Deborah L Stone; Maria L Turner; Suvimol Hill; John A Butman; Rayfel Schneider; Paul Babyn; Hatem I El-Shanti; Elena Pope; Karyl Barron; Xinyu Bing; Arian Laurence; Chyi-Chia R Lee; Dawn Chapelle; Gillian I Clarke; Kamal Ohson; Marc Nicholson; Massimo Gadina; Barbara Yang; Benjamin D Korman; Peter K Gregersen; P Martin van Hagen; A Elisabeth Hak; Marjan Huizing; Proton Rahman; Daniel C Douek; Elaine F Remmers; Daniel L Kastner; Raphaela Goldbach-Mansky Journal: N Engl J Med Date: 2009-06-04 Impact factor: 91.245
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