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SNPs, linkage disequilibrium, and chronic mountain sickness in Tibetan Chinese

Authors Buroker NE, Ning XH, Zhou ZN, Li K, Cen WJ, Wu XF, Zhu WZ, Scott CR, Chen SH

Received 23 July 2016

Accepted for publication 8 March 2017

Published 14 July 2017 Volume 2017:5 Pages 67—74


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Dörthe Katschinski

Norman E Buroker,1 Xue-Han Ning,1,2,† Zhao-Nian Zhou,3 Kui Li,4 Wei-Jun Cen,4 Xiu-Feng Wu,3 Wei-Zhong Zhu,5 C Ronald Scott,1 Shi-Han Chen1

1Department of Pediatrics, University of Washington, 2Division of Cardiology, Seattle Children’s Hospital Research Foundation, Seattle, WA, USA; 3Laboratory of Hypoxia Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; 4Lhasa People Hospital, Lhasa, Tibet; 5Center for Cardiovascular Biology and Regenerative Medicine, University of Washington, Seattle, WA, USA

Xue-Han Ning passed away on April 20, 2015

Abstract: Chronic mountain sickness (CMS) is estimated at 1.2% in Tibetans living at the Qinghai–Tibetan Plateau. Eighteen single-nucleotide polymorphisms (SNPs) from nine nuclear genes that have an association with CMS in Tibetans have been analyzed by using pairwise linkage disequilibrium (LD). The SNPs included are the angiotensin-converting enzyme (rs4340), the angiotensinogen (rs699), and the angiotensin II type 1 receptor (AGTR1) (rs5186) from the renin–angiotensin system. A low-density lipoprotein apolipoprotein B (rs693) SNP was also included. From the hypoxia-inducible factor oxygen signaling pathway, the endothetal Per-Arnt-Sim domain protein 1 (EPAS1) and the egl nine homolog 1 (ENGL1) (rs480902) SNPs were included in the study. SNPs from the vascular endothelial growth factor (VEGF) signaling pathway included are the v-akt murine thymoma viral oncogene homolog 3 (rs4590656 and rs2291409), the endothelial cell nitric oxide synthase 3 (rs1007311 and rs1799983), and the (VEGFA) (rs699947, rs34357231, rs79469752, rs13207351, rs28357093, rs1570360, rs2010963, and rs3025039). An increase in LD occurred in 40 pairwise comparisons, whereas a decrease in LD was found in 55 pairwise comparisons between the controls and CMS patients. These changes were found to occur within and between signaling pathways, which suggests that there is an interaction between SNP alleles from different areas of the genome that affect CMS.

Keywords: HAS, Qinghai-Tibetan Plateau, RAS, HIF, VEGF, pathways, miRNA

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