A large-scale replication study for the association of rs17039192 in HIF-2α with knee osteoarthritis

Osteoarthritis (OA) is a common disease with a genetic component for its etiology. Recently, a genetic association of a single nucleotide polymorphism (SNP), rs17039192 in HIF-2α with knee OA has been reported in a Japanese population; however, controversy exits for its replication and a role of HIF-2α in OA. This study aimed to evaluate the association of the SNP by a large-scale replication study. A total of 8,457 subjects (3,129 OA cases and 5,328 controls) from seven independent cohorts from six countries (Japan, China, Taiwan, Korea, Greece, and Australia) were recruited and genotyped. The association of rs17039192 with knee OA was evaluated by meta-analyses. The association of the HIF-2α SNP was not replicated in any of the populations. Contrary to the previous report, the odds ratios (ORs) of the risk allele frequency were all less than 1. A combined analysis for the seven populations also showed no replication of the association (OR = 0.91, 95% confidence interval = 0.81-1.03). Our large-scale meta-analysis showed that the association of rs17039192 in HIF-2α with knee OA is negative. The significance of HIF-2α in human OA (idiopathic OA as a common disease) should be further evaluated carefully.