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Testing the druggable EDG2 knee OA genetic factor for replication in a wide range of sample collections
  1. Rebeca Dieguez-Gonzalez (rebecadg{at}usc.es)
  1. Hospital Clinico Universitario Santiago. Santiago de Compostela, Spain
    1. Manuel Calaza
    1. Hospital Clinico Universitario Santiago. Santiago de Compostela, Spain
      1. Dongquan Shi
      1. Drum Tower Hospital Affiliated to Medical School of Nanjing University, China
        1. Ingrid Meulenbelt
        1. Leiden University Medical Center, Netherlands
          1. John Loughlin
          1. Newcastle University, United Kingdom
            1. Aspasia Tsezou
            1. University of Thessaly, Greece
              1. Jin Dai
              1. Drum Tower Hospital Affiliated to Medical School of Nanjing University, China
                1. Konstantinos N Malizos
                1. University of Thessaly, Greece
                  1. Eline P Slagboom
                  1. Leiden University Medical Center, Netherlands
                    1. Margreet Kloppenburg
                    1. Leiden University Medical Center, Netherlands
                      1. Kay Chapman
                      1. University of Oxford, Botnar Research Centre, United Kingdom
                        1. Qing Jiang
                        1. Drum Tower Hospital Affiliated to Medical School of Nanjing University, China
                          1. Dennis Kremer
                          1. Leiden University Medical Center, Netherlands
                            1. Juan J Gomez-Reino
                            1. Hospital Clinico Universitario Santiago. Santiago de Compostela, Spain
                              1. Nasahiro Nakajima
                              1. Center for Genomic Medicine, RIKEN, Tokyo, Japan
                                1. Shiro Ikegawa
                                1. Center for Genomic Medicine, RIKEN, Tokyo, Japan
                                  1. Antonio Gonzalez (antonio.gonzalez.martinez-pedrayo{at}sergas.es)
                                  1. Hospital Clinico Universitario Santiago. Santiago de Compostela, Spain

                                    Abstract

                                    Objectives: To replicate a previously reported association with OA of the promoter SNP rs10980705 in the endothelial differentiation gene 2 (EDG2).

                                    Methods: Five collections of samples, four from Europe and one from China, were studied. They included patients with three OA phenotypes: 1501 with knee OA, 1497 with hip OA and 376 with generalized OA. A total of 2521 controls were also studied. Allele and genotype frequencies of the rs10980705 SNP were analyzed in each individual sample collection and in pooled data. In addition, a meta-analysis to incorporate results from the original Japanese report was done.

                                    Results: The association of the rs10980705 SNP with knee OA was not replicated in any of the five sample collections studied or in their combined analysis (O.R. = 1.10, 95 % C.I. = 0.98 -1.22; P = 0.10). Meta-analysis of all data, including the original Japanese study, did show association with knee OA (OR = 1.15, 95 % C.I. = 1.06-1.26; P = 0.0016) but the effect was accounted for by the Japanese data and was less significant than the original report. No association was found with hip OA or with generalized OA.

                                    Conclusions: The original report of a promising genetic association between a druggable G-protein coupled receptor, EDG2, and knee OA has not been replicated. This lack of replication could be due to a modest effect of the promoter polymorphism that will require even larger studies (the winners curse) although a more pronounced effect in the Asian population versus Europeans cannot be excluded.

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                                    • Web only appendix 68:6;1017-1021

                                      • Web only appendix 68:6;1017-1021

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