title: The susceptibility gene screening in a Chinese high-altitude pulmonary edema family by whole-exome sequencing.
abstract: High-altitude pulmonary edema (HAPE) is one of idiopathic mountain sicknesses that occur in healthy lowlanders when they quickly ascend to altitudes exceeding 2500 m above sea levels within 1-7 days. Growing evidence suggests that genetics plays an important role in the risk of HAPE. In this study, we recruited a Chinese HAPE family and screened genetic variations in the 7 family members (including 6 family members with a medical history of HAPE and the propositus's mother) by whole-exome sequencing. The results showed 18 genetic variations (9 SNVs and 9 Indels) were related to HAPE. Two SNV sites (CFHR4 (p.L85F) and OXER1 (p.R176C)) were predicted to be damaging and alter protein functions by SIFT, PolyPhen-2 and PROVEAN software. The biological function of OXER1 was highly related to the hypoxia-inducible factor pathway. Therefore, those two sites were identified as candidate pathological variations. Moreover, other SNVs (NMB p.S150P, APOB p.I4194T, EIF4ENIF1 p.Q763P) and Indels (KCNJ12 p.EE333-334E, ANKRD31 p.LMN251-253LN, OR2A14 p.HFFC175-178HFC) were also predicted to be damaging as well, which also might be considered as potential candidate pathological variations related to HAPE. Collectively we firstly screened the susceptibility genes in a Chinese HAPE family by whole-exome sequencing, which will provide new clues for further mechanistic studies of HAPE.
authors.affiliation: Research Center for High Altitude Medical Science, Qinghai University School of Medicine, Xining 810001, China; Basic and Applied Key Laboratory for High Altitude Medical Science and Technology of Qinghai, Xining 810001, China; Qinghai-Utah United Key Laboratory for High Altitude Medical Science, Xining 810001, China.
authors.forename: Ying-zhong
authors.initials: YZ
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Qinghai Provincial People's Hospital, Xining 810007, China.
authors.forename: Ya-ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Qinghai University School of Medicine, Xining 810001, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Research Center for High Altitude Medical Science, Qinghai University School of Medicine, Xining 810001, China; Basic and Applied Key Laboratory for High Altitude Medical Science and Technology of Qinghai, Xining 810001, China; Qinghai-Utah United Key Laboratory for High Altitude Medical Science, Xining 810001, China.
authors.forename: Ri-li
authors.initials: RL
authors.lastname: Ge
mesh_terms: D000532:Altitude Sickness / Q000209:etiology / Q000235:genetics*; D059472:Exome; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics*; D017422:Sequence Analysis, DNA