原著
Gene-gene Interaction Between EPAS1 and EGLN1 in Patients with High-Altitude Pulmonary Edema
2015 年 63 巻 3 号 p. 157-165
詳細
2015 年 63 巻 3 号 p. 157-165
Objective : Endothelial PER-ARNT-SIM (PAS) domain protein 1 (EPAS1, also known as HIF2α) and egl nine homolog 1 (EFLN1), also known as prolyl hydroxylase domain protein 2 (PHD2), have key functions in the upstream of the hypoxia-inducible factor (HIF) pathway. In order to dissect the genetic biology of susceptibility to high-altitude pulmonary edema (HAPE) from the viewpoint of the HIF pathway, we identified the allelic discriminations of three significant tag single-nucleotide polymorphisms (SNPs) in EPAS1 and three tag SNPs in EGLN1 in HAPE-susceptible (HAPE-s) Japanese subjects.
Methods : Alleles were determined for the six SNPs (rs13419896, rs4953354, and rs4953388 in EPAS1 ; rs1435166, rs7542797, and rs2153364 in EGLN1) by the TaqMan® SNP Genotyping Assay in a group of 59 HAPE-s subjects and a control group of 67 HAPE resistant (HAPE-r) subjects. In addition to the case-control analysis, multi-dimensional reduction (MDR) methodology was applied to a gene-gene interaction analysis to evaluate the association of HAPE-s with gene-gene interactions.
Results : The EGLN1 rs2153364 (A/G) x EPAS1 rs13419896 (G/A) interaction was significantly associated with HAPE-s in the pairwise model (P＝0.0049) based on the balanced accuracy of 63.23% in MDR. However, no significance was detected for the association with HAPE-s in the single gene model.
Conclusion : The EPAS1-EGLN1 interaction appears to be associated with HAPE-s in the Japanese population despite the individual genes not being associated with HAPE-s.
