title: Variants of the low oxygen sensors EGLN1 and HIF-1AN associated with acute mountain sickness.
abstract: Two low oxygen sensors, Egl nine homolog 1 (EGLN1) and hypoxia-inducible factor 1-α inhibitor (HIF-1AN), play pivotal roles in the regulation of HIF-1α, and high altitude adaption may be involved in the pathology of acute mountain sickness (AMS). Here, we aimed to analyze single nucleotide polymorphisms (SNPs) in the untranslated regions of the EGLN1 and HIF-1AN genes and SNPs chosen from a genome-wide adaptation study of the Han Chinese population. To assess the association between EGLN1 and HIF-1AN SNPs and AMS in a Han Chinese population, a case-control study was performed including 190 patients and 190 controls. In total, thirteen SNPs were genotyped using the MassARRAY® MALDI-TOF system. Multiple genetic models were tested; The Akaike's information criterion (AIC) and Bayesian information criterion (BIC) values indicated that the dominant model may serve as the best-fit model for rs12406290 and rs2153364 of significant difference. However, these data were not significant after Bonferroni correction. No significant association was noted between AMS and rs12757362, rs1339894, rs1361384, rs2009873, rs2739513 or rs2486729 before and after Bonferroni correction. Further haplotype analyses indicated the presence of two blocks in EGLN1; one block consists of rs12406290-rs2153364, located upstream of the EGLN1 gene. Carriers of the "GG" haplotype of rs12406290-rs2153364 exhibited an increased risk of AMS after adjustments for age and smoking status. However, no significant association was observed among HIF-1AN 3'-untranslated region (3'-UTR) polymorphisms, haplotype and AMS. Our study indicates that variants in the EGLN1 5'-UTR influence the susceptibility to AMS in a Han Chinese population.
authors.affiliation: Institute of Cardiovascular Diseases of People's Liberation Army, Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. zhangeh@tmmu.edu.cn.
authors.forename: Enhao
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Diseases of People's Liberation Army, Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. sailingz@gmail.com.
authors.forename: Jihang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Diseases of People's Liberation Army, Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Jun_Jin@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Jin
authors.affiliation: Institute of Cardiovascular Diseases of People's Liberation Army, Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Qinjun198@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Institute of Cardiovascular Diseases of People's Liberation Army, Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. lihuijie001@163.com.
authors.forename: Huijie
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Diseases of People's Liberation Army, Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. huanglan198@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000532:Altitude Sickness / Q000235:genetics*; D003710:Demography; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008957:Models, Genetic; D010100:Oxygen / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D012984:Software; D055815:Young Adult
chemical_list: D012097:Repressor Proteins; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; C490190:EGLN1 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D010100:Oxygen