Genetic contribution to radiographic severity in osteoarthritis of the knee
Valdes, Ana M., Doherty, Sally A., Muir, Kenneth, Zhang, Weiya, Maciewicz, Rose A., Wheeler, Margaret, Arden, N., Cooper, Cyrus and Doherty, Michael. (2012) Genetic contribution to radiographic severity in osteoarthritis of the knee. Annals of the Rheumatic Diseases, Vol.71 (No.9). pp. 1537-1540. ISSN 0003-4967
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Official URL: http://dx.doi.org/10.1136/annrheumdis-2012-201382
Objective Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p<5×10–8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases.
Methods 3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and MCF2L genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index.
Results No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to MCF2L was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The GDF5 single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (β=0.05 (95% CI 0.02 to 0.08) p=0.0011).
Conclusions Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors.
|Item Type:||Journal Article|
|Subjects:||Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine
|Divisions:||Faculty of Medicine > Warwick Medical School > Health Sciences
Faculty of Medicine > Warwick Medical School
|Library of Congress Subject Headings (LCSH):||Osteoarthritis -- Genetic aspects, Knee -- Diseases -- Genetic aspects|
|Journal or Publication Title:||Annals of the Rheumatic Diseases|
|Page Range:||pp. 1537-1540|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Seventh Framework Programme (European Commission) (FP7)|
1. Lopez AD, Mathers CD, Ezzati M, et al. Global and regional burden of disease
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