El grupo génico interleukin-1 asociado con signos radiográficos de osteoartritis

Ingrid Meulenbelt 1 *, Albert B. Seymour 2, Marja Nieuwland 1, Tom W. J. Huizinga 1, Cornelia M. van Duijn 3, P. Eline Slagboom 1 1Leiden University Medical Center, Leiden, The Netherlands 2Discovery Pharmacogenomics, Pfizer Global Research & Development, Groton, Connecticut 3Erasmus University Medical School, Rotterdam, The Netherlands

Abstract

Objective To study the role of the interleukin-1 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).