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.