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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.

Type

Journal article

Journal

Annals of the rheumatic diseases

Publication Date

09/2012

Volume

71

Pages

1537 - 1540

Addresses

Correspondence to Dr Ana M Valdes, Kings College London, Twin Research Unit, St Thomas Hospital, Lambeth Palace Rd, London SE1 7EH, UK. ana.valdes@kcl.ac.uk

Keywords

Humans, Osteoarthritis, Knee, Guanine Nucleotide Exchange Factors, Adaptor Proteins, Vesicular Transport, Risk Factors, Genotype, Polymorphism, Single Nucleotide, Aged, Female, Male, Growth Differentiation Factor 5, Rho Guanine Nucleotide Exchange Factors