Associations of high altitude polycythemia with polymorphisms in EPAS1, ITGA6 and ERBB4 in Chinese Han and Tibetan populations

High altitude polycythemia (HAPC) is a common chronic disease at high altitude, which is characterized by excessive erythrocytosis (females, hemoglobin ≥ 190 g/L; males, hemoglobin ≥ 210 g/L). It is the most common disease in chronic mountain sickness casued primarily by persistent arterial hypoxia and ventilatory impairment. However, the disease is still unmanageable and related molecular mechanisms remain largely unclear. This study aims to explore the genetic basis of HAPC in the Chinese Han and Tibetan populations. Subjects were screened for HAPC using the latest approved diagnostic criteria. To explore the hereditary basis of HAPC and investigate the association between three genes (EPAS1, ITGA6, ERBB4) and HAPC in Chinese Han and Tibetan populations. We enrolled 100 patients (70 Han, 30 Tibetan) with HAPC and 100 healthy control subjects (30 Han, 70 Tibetan). Subjects were screened for HAPC using the latest approved diagnostic criteria combined with excessive erythrocytosis and clinical symptoms. Analysis of variance was used to evaluate the impact of polymorphism on HAPC based on genetic variation. The Chi-squared test and analyses of genetic models, rs75591953 and rs75984373 in EPAS1, rs6744873 in ITGA6, rs17335043 in ERBB4 showed associations with reduced HAPC susceptibility in Han populations. Additionally, in Tibetan populations, rs3749148 in ITGA6, rs934607 and rs141267844 in ERBB4 showed a reduced risk of HAPC, whereas rs6710946 in ERBB4 increased the risk of HAPC. Our study suggest that the polymorphisms in the EPAS1, ITGA6 and ERBB4 correlate with susceptibility to HAPC.