Whole-exome sequencing in searching for novel variants associated with the development of high altitude pulmonary edema

Mingyue Chen; Faling Yi; Yijin Qi; Beibei Zhao; Zhanhao Zhang; Xue He; Dongya Yuan; Tianbo Jin

doi:10.1016/j.gene.2023.147384

Whole-exome sequencing in searching for novel variants associated with the development of high altitude pulmonary edema

Gene. 2023 Jun 20:870:147384. doi: 10.1016/j.gene.2023.147384. Epub 2023 Mar 29.

Authors

Mingyue Chen¹, Faling Yi¹, Yijin Qi¹, Beibei Zhao¹, Zhanhao Zhang¹, Xue He¹, Dongya Yuan², Tianbo Jin³

Affiliations

¹ Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China; School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China.
² Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China; School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China. Electronic address: dy62@163.com.
³ Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China; School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, Shaanxi 710069, China; Shaanxi Provincial Key Laboratory of Biotechnology, Northwest University, Xi'an, Shaanxi 710069, China. Electronic address: jintb@xzmz.edu.cn.

PMID: 37001572
DOI: 10.1016/j.gene.2023.147384

Abstract

Background: High altitude pulmonary edema (HAPE) is a high-altitude idiopathic disease with serious consequences due to hypoxia at high altitude, and there is individual genetic susceptibility. Whole-exome sequencing (WES) is an effective tool for studying the genetic etiology of HAPE and can identify potentially novel mutations that may cause protein instability and may contribute to the development of HAPE.

Materials and methods: A total of 50 unrelated HAPE patients were examined using WES, and the available bioinformatics tools were used to perform an analysis of exonic regions. Using the Phenolyzer program, disease candidate gene analysis was carried out. SIFT, PolyPhen-2, Mutation Taster, CADD, DANN, and I-Mutant software were used to assess the effects of genetic variations on protein function.

Results: The results showed that rs368502694 (p. R1022Q) located in NOS3, rs1595850639 (p. G61S) located in MYBPC3, and rs1367895529 (p. R333H) located in ITGAV were correlated with a high risk of HAPE, and thus could be regarded as potential genetic variations associated with HAPE.

Conclusion: WES was used in this study for the first time to directly screen genetic variations related to HAPE. Notably, our study offers fresh information for the subsequent investigation into the etiology of HAPE.

Keywords: Genetic predisposition to disease; High altitude pulmonary edema; Variant prioritization; Whole-exome sequencing.

MeSH terms

Altitude
Altitude Sickness* / genetics
Exome Sequencing
Humans
Pulmonary Edema* / genetics

Supplementary concepts

Pulmonary edema of mountaineers