Evidence for genetic anticipation in nodal osteoarthritis

Wright, Gary; Regan, Marian; Deighton, Chris; Wallis, Gillian A.; Doherty, Michael

doi:10.1136/ard.57.9.524

Cited by 21 publications

(13 citation statements)

References 14 publications

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“…It has been demonstrated that genetic factors also play an important role in late-onset OA. Familial aggregation of OA (especially hand, knee, and hip OA) was observed in population-based studies (1)(2)(3)(4). Candidate genes that may exert this genetic influence have been investigated by means of population-based association studies and genetic linkage studies in OA families.…”

Section: Discussionmentioning

confidence: 99%

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

Meulenbelt

Seymour

Nieuwland

et al. 2004

Arthritis & Rheumatism

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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). Conclusion.Our findings suggest that the IL-1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.Osteoarthritis (OA) is a joint disease characterized by degeneration of articular cartilage and remodeling of the subchondral bone with sclerosis. It has been demonstrated that genetic factors also play an important role in late-onset OA. Familial aggregation of OA (especially hand, knee, and hip OA) was observed in population-based studies (1-4). Candidate genes that may exert this genetic influence have been investigated by means of population-based association studies and genetic linkage studies in OA families. A large number of association studies using various definitions of OA have been performed, mainly investigating genes encoding structural proteins of the extracellular matrix of cartilage (e.g., COL2A1, CRTM, and AGN) or genes playing a role in the regulation of bone density and mass (e.g., VDR, IGF1, and ER), and have shown both positive and negative results for each of the genes (for review, see ref. 5). These differences in study results may indicate either false-positive or false-negative results, could be the result of differences in the OA phenotype investigated, or could be attributable to different linkage disequilibrium (LD) between the associated polymorphism and the causal mutation in various populations. Moreover, it is becoming increasingly clear that the genetic risk factors for OA at different joint sites may be distinct (6).Several groups of investigators have performed genome-wide screens of sibling pairs or nuclear families with OA and reported multiple chromosome areas (e.g., 2p24, 3p12, 4q32, 11q12, 4q27, Xp11.3, and 7p22) that show positive linkage to specific OA phenotypes, such as radiographic OA (ROA) in the distal interphalangeal (DIP) joints, s...

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Section: Discussionmentioning

confidence: 99%

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

Meulenbelt

Seymour

Nieuwland

et al. 2004

Arthritis & Rheumatism

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“…Erosive OA was defined as the presence of erosive radiographic features according to the Verbruggen–Veys score in at least two IP joints 14. Nodal OA was defined as the presence of Heberden or Bouchard nodes affecting at least two rays of either hand 15. The last subset comprises symptomatic thumb base OA, which was defined as the presence of pain or stiffness in the CMC-1 joint on most of the days of the preceding month.…”

Section: Methodsmentioning

confidence: 99%

Clinical and radiographic disease course of hand osteoarthritis and determinants of outcome after 6 years

Bijsterbosch

Watt

Meulenbelt

et al. 2010

Annals of the Rheumatic Diseases

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“…Nodal OA was defined as Heberden's or Bouchard's nodes assessed by palpation affecting ≥2 rays of either hand 15. The number of nodes refers to the number of IP joints with nodes.…”

Section: Methodsmentioning

confidence: 99%