title: Genetic variants of endothelial PAS domain protein 1 are associated with susceptibility to acute mountain sickness in individuals unaccustomed to high altitude: A nested case-control study.
abstract: The endothelial PAS domain protein 1 (EPAS1) gene functions to sense the blood oxygen level by regulating the hypoxia-inducible transcription factor pathway, and single nucleotide polymorphisms (SNPs) ofEPAS1have been found to have a strong and positive selection in the adaptation of the native Tibetan highland population to high-altitude hypoxia. The aim of the present study was to investigate the effect ofEPAS1SNPs on the risk of acute mountain sickness (AMS) and the physiological responses to acute high-altitude hypoxia in lowland humans. Three tag SNPs (rs6756667, rs13419896 and rs4953354; minor allele frequency, ≥5%) were selected and genotyped in 603 unrelated Han Chinese men, who had traveled to Lhasa (a high-altitude hypoxia environment) by plane, using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. The data showed that theEPAS1rs6756667 wild-type GG homozygous genotype was associated with elevated AMS risk compared with the AA and AG genotypes (odds ratio, 1.815; 95% confidence interval, 1.233-2.666; P=0.0023) using the dominant-model analysis.EPAS1rs6756667 GG genotypes were also associated with higher levels of hemoglobin, red blood cells and hematocrit than those carrying the AG heterozygote during AMS development. These findings indicate thatEPAS1SNPs play a role in the physiological effects of AMS, and these effects could be further evaluated as a therapeutic strategy to control acute hypoxia-related human diseases.
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Guo
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Jihang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jin
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Xubin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Geng
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Department of Cardiology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
keywords: acute mountain sickness; endothelial PAS domain protein 1; hypoxia; single nucleotide polymorphisms