Human Molecular Genetics Advance Access published online on January 30, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp053
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LARGE REPLICATION STUDY AND META-ANALYSES OF DVWA AS AN OSTEOARTHRITIS SUSCEPTIBILITY LOCUS IN EUROPEAN AND ASIAN POPULATIONS
1 Department of Molecular Epidemiology Leiden University Medical Center, 2300 RC, Leiden, The Netherlands 2 Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Center, University of Oxford, OX3 7LD, Oxford, UK 3 Laboratorio Investigacion and Rheumatology Unit. Hospital Clinico Universitario Santiago, 15706-Santiago de Compostela. Spain 4 The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China 5 Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University. Nanjing 210061, Jiangsu, China 6 Dept. of Biology and Genetics, University of Thessaly, Larissa, Greece 7 Dept. of Orthopaedics, University of Thessaly, Larissa, Greece 8 Institute for Biomedical Research and Technology, University of Thessaly, Larissa, Greece 9 Dept of Rheumatology & Department of Clinical Epidemiology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands 10 Department of Medicine. University of Santiago de Compostela, 15706-Santiago de Compostela, Spain 11 Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo 108-8639, Japan 12 Newcastle University, Musculoskeletal Research Group, Institute of Cellular Medicine, New Castle, UK
* Corresponding author: Ingrid Meulenbelt, Section Molecular Epidemiology, Leiden University Medical Centre, Postzone S-05-P, PO Box 9600, 2300 RC Leiden, The Netherlands, Tel. +31 71 526 9734; Fax +31 71 526 8280, E-mail: i.meulenbelt{at}lumc.nl
Received December 9, 2008; Revised January 26, 2009; Accepted January 26, 2009
Recently, through a genome wide association study in Japanese knee osteoarthritis (OA) cases, a previously unknown gene, DVWA, was identified. The non-synonymous SNP rs7639618 was subsequently found to be consistent and most significantly associated in Japanese and Han Chinese knee OA studies and functional relevant. Here the association of the DVWA polymorphisms (rs7639618, rs11718863 and rs9864422) were genotyped in 1120 knee OA cases, 1482 hip OA cases and 2147 controls, all of white European descent from the Netherlands, the UK, Spain and Greece. Random effect DerSimonian and Laird meta-analyses were performed to assess association in the different strata. To assess a more global effect the original Japanese and Chinese data was included with the European. The meta-analyses provided evidence for global association of rs7639618 with knee OA with an odds ratio (OR) of 1.29, 95% confidence interval (CI) of 1.15 -1.45 and P of 2.70x10–5. This effect, however, showed moderate heterogeneity and rs7639618 was not independently associated with knee OA in Europeans, with an OR of 1.16, 95% CI of 0.99 - 1.35 and P of 0.063. Furthermore, no association was observed with hip OA in Europeans, with a P of 0.851. Our results suggests that there may be global relevance for the DVWA SNP rs7639618 among knee OA cases, however, the apparent lower effect size in combination with the higher risk allele frequency in the European samples highlights again the ethnic differences in effects of discovered OA susceptibility genes.