Correlation between single nucleotide polymorphisms in hypoxia-related genes and susceptibility to acute high-altitude pulmonary edema

Abstract

ABSTRACT. This study aimed to explore the relationship between genetic changes and high-altitude pulmonary edema (HAPE) susceptibility, and to screen for the key single nucleotide polymorphism (SNP) loci in the HAPE-susceptibility gene, by investigating the SNPs occurring in hypoxia-related genes in HAPE-susceptible and control (non-susceptible) populations. This research was conducted on Han recruits, who travelled to the Lhasa plateau (altitude, 3658 m). Ten loci located on ten genes extracted from the HAPE and healthy populations were amplified by polymerase chain reaction, and subsequently sequenced. The investigated genes included those coding for aldosterone synthase 2 (CYP11B2), angiotensin-converting enzyme (ACE), heat-shock protein 70 (HSP70), nuclear factor kappa B (NF-κB), surfactant protein A2 (SP-A2), plasminogen activator inhibitor-1 (PAI-1), nitric oxide synthetase (NOS), vascular endothelial growth factor (VEGF), prolyl hydroxylase (EGLN1), and zinc finger protein A20. The gene distribution of each SNP loci and its correlation with (2015) HAPE was analyzed. Statistical analyses of the genotype frequencies of the SNPs revealed significant differences in the ACE (rs4309), EGLN1 (rs480902), SP-A2 (rs1965708), HSP70 (rs1008438), PAI-1 (rs1799889), and NOS (rs199983) expressions between the HAPE and healthy control groups (P < 0.05); therefore, these SNP loci were believed to indicate HAPE susceptibility. HAPE is correlated with multiple-SNP loci. A correlation analysis between genetic polymorphism and HAPE susceptibility revealed that 6 hypoxia-related genes were key sites accounting for HAPE. These findings could help assess the risk of HAPE in populations expressing different genotypes, in order to reduce the occurrence of HAPE.

Hypoxia Inducible Factor-2 Alpha and Prolinhydroxylase 2 Polymorphisms in Patients with Acute Respiratory Distress Syndrome (ARDS)

“…Wu et al showed a correlation between single nucleotide polymorphisms in hypoxia-related genes like the PHD2 (SNPrs480902) and susceptibility to acute high-altitude pulmonary edema (HAPE). They found that the HAPE cases had a significant higher T-allele frequency than the control group [25]. Buroker et al described phenotypical differences between Han Chinese with acute mountain sickness (AMS) in the rs480902 SNP.…”

Differences in Tolerance to Hypoxia: Physiological, Biochemical, and Molecular-Biological Characteristics

“…People could be distinguished by significant individual variability in the expression levels of HIF and other HIF-dependent genes in leukocytes, which indicates phenotypic differences in its regulation. It was demonstrated that there is individual variability in the expression of HIF and its dependent genes in response to hypoxic or inflammatory stimuli, which, at least in part, is due to genetic polymorphisms [ 7 , 75 , 76 , 77 , 78 , 79 ].…”

A case‐control study of the genetic polymorphism of IL6 and HAPE risk in a Chinese Han population

“…The exact mechanism underlying the development of HAPE remains unclear, although exaggerated pulmonary hypertension has been suggested to play a crucial important role . There’s a segment of the population affected individuals develop HAPE while exposed to high altitudes, probably due to individual variations and several genetic studies have demonstrated that a genetic susceptibility may play a role in the development of HAPE . The genetic susceptibility and the HAPE risk have been reported, including polymorphisms of the genes of NOS3, ACE, AGTR1, ADRB2, HLA， VEGF et al have been positively associated with HAPE.…”

“…5 There's a segment of the population affected individuals develop HAPE while exposed to high altitudes, probably due to individual variations and several genetic studies have demonstrated that a genetic susceptibility may play a role in the development of HAPE. 6,7 The genetic susceptibility and the HAPE risk have been reported, including polymorphisms of the genes of NOS3, 8 ACE, 9 AGTR1, 10 ADRB2, 11 HLA, 12 VEGF 13 At present, studies have been found that HAPE may have an important pathogenesis of inflammation. The roles of these cytokines in the development of HAPE are complicated.…”