Association of EPAS1 and PPARA Gene Polymorphisms with High-Altitude Headache in Chinese Han Population

Abstract

Background. High-altitude headache (HAH) is the most common complication after high-altitude exposure. Hypoxia-inducible factor- (HIF-) related genes have been confirmed to contribute to high-altitude acclimatization. We aim to investigate a possible association between HIF-related genes and HAH in the Chinese Han population. Methods. In total, 580 healthy Chinese Han volunteers were recruited in Chengdu (500 m) and carried to Lhasa (3700 m) by plane in 2 hours. HAH scores and basic physiological parameters were collected within 18–24 hours after the arrival. Thirty-five single nucleotide polymorphisms (SNPs) in HIF-related genes were genotyped, and linkage disequilibrium (LD) was evaluated by Haploview software. The functions of SNPs/haplotypes for HAH were developed by using logistic regression analysis. Results. In comparison with wild types, the rs4953354 “G” allele (P=0.013), rs6756667 “A” allele (P=0.036) in EPAS1, and rs6520015 “C” allele in PPARA (P=0.009) were significantly associated with decreased risk of HAH. The rs7292407-rs6520015 haplotype “C-C” in PPARA was identified as a protective factor (P=0.030). Importantly, EPAS1 and PPARA genes have synergistic effects in decreasing HAH risk (P=0.003). Conclusions. EPAS1 and PPARA polymorphisms were associated with HAH in the Chinese Han population. Our findings pointed out potentially predictive gene markers, provided new insights into understanding pathogenesis, and may further provide prophylaxis and treatment strategies for HAH.

The role of EPAS1 polymorphisms on COPD susceptibility in southern Chinese

“…Initially, EPAS1 attracted widespread attention for its important role in Tibetans' adaptation to hypoxia [ 35 , 36 ]. Subsequently, several studies reported that EPAS1 polymorphisms modified the susceptibility to multiple acute altitude sicknesses when Han Chinese rapidly entered the plateau [ 20 , [37] , [38] , [39] , [40] ]. For example, the rs6756667 A allele reduced the risk of acute high-altitude headache and acute appetite loss [ 38 , 40 ], while the rs13419896 A allele made Han Chinese susceptible to acute cardiorespiratory fitness impairment [ 37 ].…”

“…Subsequently, several studies reported that EPAS1 polymorphisms modified the susceptibility to multiple acute altitude sicknesses when Han Chinese rapidly entered the plateau [ 20 , [37] , [38] , [39] , [40] ]. For example, the rs6756667 A allele reduced the risk of acute high-altitude headache and acute appetite loss [ 38 , 40 ], while the rs13419896 A allele made Han Chinese susceptible to acute cardiorespiratory fitness impairment [ 37 ]. As the research continues to deepen, researchers also observed that the rs13419896 A allele is a risk factor for premature retinopathy, lung cancer, hepatitis B, and liver cirrhosis [ 21 , [41] , [42] , [43] ].…”