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Genetic contribution to radiographic severity in osteoarthritis of the knee

Genetic contribution to radiographic severity in osteoarthritis of the knee
Genetic contribution to radiographic severity in osteoarthritis of the knee
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 (?=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
0003-4967
1537-1540
Valdes, Ana M.
4e4c3f14-3895-4129-94ca-f4176dd83e94
Doherty, Sally
8353b108-3045-464b-be45-e3661d81481e
Muir, Kenneth R.
4703d677-d4f5-4386-aa1e-2de40e31354f
Zhang, Weiya
9997b6da-0a49-4a50-bab4-dcb94bd9c151
Maciewicz, Rose A.
c33d1ff0-a737-472e-9f30-ad5ac6bafa28
Wheeler, Margaret
b8cad0c8-0f79-48e5-ae09-636fecb1e2c8
Arden, Nigel
23af958d-835c-4d79-be54-4bbe4c68077f
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Doherty, M.
3ccd8b47-e119-4f38-b813-08e9036a9ff3
Valdes, Ana M.
4e4c3f14-3895-4129-94ca-f4176dd83e94
Doherty, Sally
8353b108-3045-464b-be45-e3661d81481e
Muir, Kenneth R.
4703d677-d4f5-4386-aa1e-2de40e31354f
Zhang, Weiya
9997b6da-0a49-4a50-bab4-dcb94bd9c151
Maciewicz, Rose A.
c33d1ff0-a737-472e-9f30-ad5ac6bafa28
Wheeler, Margaret
b8cad0c8-0f79-48e5-ae09-636fecb1e2c8
Arden, Nigel
23af958d-835c-4d79-be54-4bbe4c68077f
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Doherty, M.
3ccd8b47-e119-4f38-b813-08e9036a9ff3

Valdes, Ana M., Doherty, Sally, Muir, Kenneth R., Zhang, Weiya, Maciewicz, Rose A., Wheeler, Margaret, Arden, Nigel, Cooper, Cyrus and Doherty, M. (2012) Genetic contribution to radiographic severity in osteoarthritis of the knee. Annals of the Rheumatic Diseases, 71 (9), 1537-1540. (doi:10.1136/annrheumdis-2012-201382). (PMID:22615457)

Record type: Article

Abstract

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 (?=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

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Published date: September 2012
Organisations: Chemistry, Faculty of Medicine

Identifiers

Local EPrints ID: 347093
URI: http://eprints.soton.ac.uk/id/eprint/347093
ISSN: 0003-4967
PURE UUID: 932e084c-6d07-4530-bc33-4b1fce7ae868
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 17 Jan 2013 11:18
Last modified: 29 Oct 2019 02:02

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