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Open Access Research article

Association of a BMP5 microsatellite with knee osteoarthritis: case-control study

Cristina Rodriguez-Fontenla1, Andrew Carr2, Juan J Gomez-Reino13, Aspasia Tsezou4, John Loughlin5 and Antonio Gonzalez1*

Author Affiliations

1 Laboratorio Investigacion 10 & Rheumatology, Instituto de Investigacion Sanitaria - Hospital Clinico Universitario de Santiago, Choupana s/n 15706, Santiago de Compostela, Spain

2 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, OX3 7HE, Oxford, UK

3 Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, San Francisco s/n, 15701, Spain

4 Department of Biology, University of Thessaly, Medical School, 22 Papakyriazi Street, 41222, Larissa, Greece

5 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE1 7RU, UK

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Arthritis Research & Therapy 2012, 14:R257  doi:10.1186/ar4102

Published: 27 November 2012

Abstract

Introduction

We aimed to explore the involvement of a multiallelic functional polymorphism in knee osteoarthritis (OA) susceptibility as a prototype of possible genetic factors escaping GWAS detection.

Methods

OA patients and controls from three European populations (Greece, Spain and the UK) adding up to 1003 patients (716 women, 287 men) that had undergone total knee joint replacement (TKR) due to severe primary OA and 1543 controls (758 women, 785 men) lacking clinical signs or symptoms of OA were genotyped for the D6S1276 microsatellite in intron 1 of BMP5. Genotype and mutiallelic trend tests were used to compare cases and controls.

Results

Significant association was found between the microsatellite and knee OA in women (P from 3.1 x10-4 to 4.1 x10-4 depending on the test), but not in men. Three of the alleles showed significant differences between patients and controls, one of them of increased risk and two of protection. The gender association and the allele direction of change were very concordant with those previously reported for hip OA.

Conclusions

We have found association of knee OA in women with the D6S1276 functional microsatellite that modifies in cis the expression of BMP5 making this a sounder OA genetic factor and extending its involvement to other joints. This result also shows the interest of analysing other multiallelic polymorphisms.