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Open Access Highly Accessed Research article

Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis

Hanneke JM Kerkhof12, Ingrid Meulenbelt23, Andrew Carr4, Antonio Gonzalez5, Deborah Hart6, Albert Hofman7, Margreet Kloppenburg8, Nancy E Lane9, John Loughlin10, Michael C Nevitt9, Huibert AP Pols1, Fernando Rivadeneira127, Eline P Slagboom23, Tim D Spector6, Lisette Stolk12, Aspasia Tsezou11, André G Uitterlinden127, Ana M Valdes6 and Joyce BJ van Meurs12*

Author Affiliations

1 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands

2 The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands

3 Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

4 Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, Oxford, UK

5 Laboratorio Investigacion and Rheumatology Unit, Hospital Clinico Universitario Santiago, Santiago de Compostela, Spain

6 Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, Kings College London, London, UK

7 Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

8 Department of Rheumatology and department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

9 University of California at San Francisco and University of California at Davis, Sacramento, USA

10 Musculoskeletal Research Group, Newcastle University, Institute of Cellular Medicine, UK

11 Department of Biology and Genetics, University of Thessaly, Larissa, Greece

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BMC Medical Genetics 2010, 11:164  doi:10.1186/1471-2350-11-164

Published: 16 November 2010



The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.


In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls.


The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05).


This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase.