title: An EPAS1 haplotype is associated with high altitude polycythemia in male Han Chinese at the Qinghai-Tibetan plateau.
abstract: BACKGROUND
  Hemoglobin concentration at high altitude is considered an important marker of high altitude adaptation, and native Tibetans in the Qinghai-Tibetan plateau show lower hemoglobin concentrations than Han people who have emigrated from plains areas. Genetic studies revealed that EPAS1 plays a key role in high altitude adaptation and is associated with the low hemoglobin concentration in Tibetans. Three single nucleotide polymorphisms (rs13419896, rs4953354, rs1868092) of noncoding regions in EPAS1 exhibited significantly different allele frequencies in the Tibetan and Han populations and were associated with low hemoglobin concentrations in Tibetans.
  
  
  METHODS
  To explore the hereditary basis of high altitude polycythemia (HAPC) and investigate the association between EPAS1 and HAPC in the Han population, these 3 single nucleotide polymorphisms were assessed in 318 male Han Chinese HAPC patients and 316 control subjects. Genotyping was performed by high resolution melting curve analysis.
  
  
  RESULTS
  The G-G-G haplotype of rs13419896, rs4953354, and rs1868092 was significantly more frequent in HAPC patients than in control subjects, whereas no differences in the allele or genotype frequencies of the 3 single nucleotide polymorphisms were found between HAPC patients and control subjects. Moreover, genotypes of rs1868092 (AA) and rs4953354 (GG) that were not observed in the Chinese Han in the Beijing population were found at frequencies of 1.6% and 0.9%, respectively, in our study population of HAPC patients and control subjects.
  
  
  CONCLUSIONS
  Carriers of this EPAS1 haplotype (G-G-G, rs13419896, rs4953354, and rs1868092) may have a higher risk for HAPC. These results may contribute to a better understanding of the pathogenesis of HAPC in the Han population.
authors.affiliation: Department of Pathophysiology and High Altitude Physiology (Drs Chen, Jiang, Liu, and Gao); Key Laboratory of High Altitude Medicine, People's Liberation Army (Drs Chen, Jiang, Luo, Liu, and Gao), Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology and High Altitude Physiology (Drs Chen, Jiang, Liu, and Gao); Key Laboratory of High Altitude Medicine, People's Liberation Army (Drs Chen, Jiang, Luo, Liu, and Gao), Chongqing, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of High Altitude Disease (Dr Luo), College of High Altitude Military Medicine, and Key Laboratory of High Altitude Medicine, Third Military Medical University, Ministry of Education; Key Laboratory of High Altitude Medicine, People's Liberation Army (Drs Chen, Jiang, Luo, Liu, and Gao), Chongqing, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pathophysiology and High Altitude Physiology (Drs Chen, Jiang, Liu, and Gao); Key Laboratory of High Altitude Medicine, People's Liberation Army (Drs Chen, Jiang, Luo, Liu, and Gao), Chongqing, China.
authors.forename: Fuyu
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology and High Altitude Physiology (Drs Chen, Jiang, Liu, and Gao); Key Laboratory of High Altitude Medicine, People's Liberation Army (Drs Chen, Jiang, Luo, Liu, and Gao), Chongqing, China. Electronic address: gaoy66@yahoo.com.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000531:Altitude; D044466:Asian People / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009051:Mountaineering; D011086:Polycythemia / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018609:Tibet / Q000453:epidemiology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: EPAS1; Qinghai-Tibetan plateau; high altitude polycythemia; high resolution melting