Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis 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).


CONCLUSIONS
Our findings suggest that the IL-1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.
Meulenbelt
Ingrid
I
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. i.meulenbelt@lumc.nl
Seymour
Albert B
AB
Nieuwland
Marja
M
Huizinga
Tom W J
TW
van Duijn
Cornelia M
CM
Slagboom
P Eline
PE
D000368:Aged; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D008875:Middle Aged; D005810:Multigene Family; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011859:Radiography; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*; D020080:Tandem Repeat Sequences
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins