Testing the druggable endothelial differentiation gene 2 knee osteoarthritis genetic factor for replication in a wide range of sample collections.
OBJECTIVE
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.
Dieguez-Gonzalez
R
R
Hospital Clinico Universitario Santiago, Santiago de Compostela, Spain.
Calaza
M
M
Shi
D
D
Meulenbelt
I
I
Loughlin
J
J
Tsezou
A
A
Dai
J
J
Malizos
K N
KN
Slagboom
E P
EP
Kloppenburg
M
M
Chapman
K
K
Jiang
Q
Q
Kremer
D
D
Gomez-Reino
J J
JJ
Nakajima
N
N
Ikegawa
S
S
Gonzalez
A
A
D000368:Aged; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020370:Osteoarthritis, Knee / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D044465:White People / Q000235:genetics
D049368:Receptors, Lysophosphatidic Acid