title: A large-scale replication study for the association of rs17039192 in HIF-2α with knee osteoarthritis.
abstract: 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.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakajima
authors.forename: Dongquan
authors.initials: D
authors.lastname: Shi
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
authors.forename: Minghao
authors.initials: M
authors.lastname: Zheng
authors.forename: Paul E
authors.initials: PE
authors.lastname: Norman
authors.forename: Ching-Heng
authors.initials: CH
authors.lastname: Chou
authors.forename: Ming Ta Michael
authors.initials: MT
authors.lastname: Lee
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D044466:Asian People / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020370:Osteoarthritis, Knee / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1