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Introduction/objectives
Articular cartilage is the target tissue of osteoarthritis (OA), and because it lacks capillary networks, the microenvironment is hypoxic. Hypoxia inducible factor-1 alpha (HIF-1α) regulates the homeostasis of this tissue. The aim of this study was to investigate whether genetic polymorphisms of the HIF-1α signaling pathway are involved in the development of knee OA.
Method
We performed a case-control association study and genotyped 134 knee OA patients and 267 healthy controls. All participants were genotyped in order to evaluate 42 SNPs from 22 genes involved in the HIF-1α signaling pathway using the OpenArray technology. Gene-gene interactions (epistasis) were analyzed using the multifactor dimensionality reduction (MDR) method.
Results
The MDR analysis showed epistasis between
AKT2
(rs8100018) and
IGF1
(rs2288377),
AKT2
(rs8100018) and
IGF1
(rs35767),
IGF1
(rs35767) and
COL2A1
(rs1793953), and between
GSK3B
(rs6438552) and
IGF1
(rs35767) polymorphisms, with information gain values of 21.24%, 8.37%, 9.93%, and 5.73%, respectively. Additionally, our model allowed us to identify high- and low-risk genotypes among
COL2A1
rs1793953,
GSK3B
rs6438552,
AKT2
rs8100018, and
IGF1
rs35767 polymorphisms.
Conclusions
Knowing the interactions of these polymorphisms involved in HIF-1α signaling pathway could provide a new diagnostic support tool to identify individuals at high risk of developing knee OA.