Abstract: Objective To identify the gene polymorphism of HIF-1α associated with hypoxic tolerance in CCHD. Methods HIF-1α was selected sequenced in 97 CCHD cases and 108 ACHD cases. Different distribution of polymorphic site was detected after bioinformatics analysis. The related variants were confirmed using Sanger Sequencing. For the polymorphic site in promoter region of HIF-1α, different genotype human HIF-1α promoter-luciferase reporter gene vectors were constructed respectively, and the vectors were transiently transfected into HEK293T and H9C2 cells. Dual-Luciferase assay was performed to reflect the transcriptional activity of different genotype HIF-1α promoter. Results The mutation rate of HIF-1α -1496 in CCHD population was significantly higher than that in ACHD population (P<0.05). Transcriptional activity of DD genotype was higher than that of AA genotype (P<0.05). Conclusions HIF-1α -1946 is associated with hypoxia tolerance of CCHD. Transcription activity of DD genotype was significantly increased, which may be one of the genetic mechanisms of hypoxia tolerance.

Key words: Key words: HIF-1α, gene polymorphism, next generation sequencing, cyanotic congenital heart disease, hypoxic