PT  - JOURNAL ARTICLE
AU  - R Dieguez-Gonzalez
AU  - M Calaza
AU  - D Shi
AU  - I Meulenbelt
AU  - J Loughlin
AU  - A Tsezou
AU  - J Dai
AU  - K N Malizos
AU  - E P Slagboom
AU  - M Kloppenburg
AU  - K Chapman
AU  - Q Jiang
AU  - D Kremer
AU  - J J Gomez-Reino
AU  - N Nakajima
AU  - S Ikegawa
AU  - A Gonzalez
TI  - Testing the druggable endothelial differentiation gene 2 knee osteoarthritis genetic factor for replication in a wide range of sample collections
AID  - 10.1136/ard.2008.093641
DP  - 2009 Jun 01
TA  - Annals of the Rheumatic Diseases
PG  - 1017--1021
VI  - 68
IP  - 6
4099  - http://ard.bmj.com/content/68/6/1017.short
4100  - http://ard.bmj.com/content/68/6/1017.full
SO  - Ann Rheum Dis2009 Jun 01; 68
AB  - Objectives: To replicate a previously reported association with osteoarthritis (OA) of the promoter single nucleotide polymorphism (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 3 OA phenotypes: 1501 with knee OA, 1497 with hip OA and 376 with generalised OA. A total of 2521 controls were also studied. Allele and genotype frequencies of the rs10980705 SNP were analysed in each individual sample collection and in pooled data. In addition, a meta-analysis to incorporate results from the original Japanese report was performed.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 (odds ratio (OR) 1.10, 95% CI 0.98 to 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% CI 1.06 to 1.26; p = 0.002) 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 generalised 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 vs Europeans cannot be excluded.