Association between single nucleotide polymorphisms in ADRB2, GNB3 and GSTP1 genes and high-altitude pulmonary edema (HAPE) in the Chinese Han population

Abstract

High altitude pulmonary edema (HAPE) occurs mainly under conditions such as high altitude, rapid ascent, or hypoxia. Previous studies suggest that ADRB2, GNB3, TH, and GSTP1 polymorphisms are associated with various lung diseases. We evaluated whether those polymorphisms are associated with the risk of HAPE in a Chinese Han population. ADRB2, GNB3, TH and GSTP1 polymorphisms were genotyped using a Sequenom MassARRAY. Logistic regression, adjusted for age and gender, was used to evaluate the association between the genotypes and the risk of HAPE by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). The results revealed that GNB3 rs4963516 allele ‘‘G’’ (G vs T: OR = 0.70, 95% CI = 0.55–0.90, p = 0.006) was associated with HAPE risk. The ADRB2 rs1042718 alleles had a 1.29-fold (95%CI = 1.00-1.66; p = 0.045) increased risk of HAPE, and the GSTP1 rs749174 alleles had a 0.71-fold (95%CI = 0.52-0.99; p = 0.042) decreased risk of HAPE. Co-dominant and dominant models of GNB3 rs4963516 decreased the risk of HAPE (p = 0.023 and p = 0.008, respectively). Our results indicate GNB3 and GSTP1 polymorphisms may protect against HAPE progression, while ADRB2 polymorphisms are associated with an increased risk of HAPE.

Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR

“…Numerous studies have focused on the mechanisms underlying high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE), prevention of altitude sickness, and adaptation to hypoxia ( Dehnert and Batsch, 2017 ; He et al., 2017 ; Jin, 2017 ). More recently, changes in drug metabolism under high-altitude hypoxia have drawn increasing scientific attention.…”

Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension

“…In cancer, GSTP1 has been found to be a tumor suppressor ( 54 ) or oncogene, depending upon the tumor of interest. Single-nucleotide variants in this gene have been associated with susceptibility to hypobaric hypoxia and high altitude pulmonary edema ( 55 , 56 ), often thought to be driven by compromise of the endothelial barrier function. GSTP1 mutations have also been linked to chronic obstructive pulmonary disease ( 57 ), a disease with clear etiologic connections to PH.…”

Effects of Plateau Air Quality and Low Oxygen Content on Platelet mtDNA Methylation and High Altitude Pulmonary Edema

“…High altitude pulmonary edema (HAPE), as a potentially fatal AMS, occurs within 2 -4 days after reaching an altitude of 3000 m or above (He et al, 2017). HAPE is a severe lung injury caused by acute HBH and its pathogenesis is still not fully clarified, which seriously impedes the development of clinical research to prevent and treat HAPE (Jin et al, 2019).…”