Human Molecular Genetics Advance Access published online on May 20, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm115
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Meta-analysis of association between the ASPN D-repeat and osteoarthritis
1 Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo 108-8639, Japan 2 The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China 3 University of Athens, Medical School, Department of Med.Genetics, Athens, Greece 4 Laboratorio de Investigacion 2, Hospital Clinico Universitario de Santiago, 15706-Santiago de Compostela, Spain 5 Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, Tokyo 108-8639, Japan 6 University of Thessalia, Medical School, Department of Biology, Larissa, Greece 7 Division of Statistical Genetics, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, Japan 8 University of Oxford, Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, United Kingdom
Corresponding author: Shiro Ikegawa, Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Tel & Fax: +81-3-5449-5393, Email: sikegawa{at}ims.u-tokyo.ac.jp
Received March 26, 2007; Revised April 26, 2007; Accepted April 26, 2007
Osteoarthritis (OA) is the most common form of human arthritis. Genetic factors have been implicated in OA. It was reported that an aspartic acid (D)-repeat polymorphism in the gene encoding asporin (ASPN) was associated with OA of knee and hip joints in Japanese; in the three independent studies performed, the D14 allele of the ASPN polymorphism was over-represented, and the D13 allele was under-represented. Subsequently, four replication studies, three in Europeans and one in Chinese populations, have been reported; however, they showed inconsistent results. To evaluate between-study heterogeneity and to estimate the common genetic effect of the D-repeat polymorphism on OA, we performed a meta-analysis of the five reports that include seven association studies, using the DerSimonian-Laird procedure. We detected association between knee OA and the susceptible D14 allele (P=0.003, summary odds ratio [OR]=1.46) with significant heterogeneity (P=0.047) among the studies. We also detected positive association between knee OA and the protective D13 allele (p=0.026, summary OR=0.84) with significant heterogeneity (P=0.040) among the studies. Because of significant heterogeneity we stratified the studies by ethnicity. We detected positive association between knee OA and the D14 allele (P=0.0000013, summary OR=1.95) with non-significant heterogeneity (P=0.535) in Asian populations. In hip OA, significant heterogeneity was identified and there was no positive association for any allele in any comparison. The present results suggest that the association of the ASPN D14 allele and knee OA has global relevance, but that its effect has ethnic differences.
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