Genome-wide association study of high-altitude pulmonary edema in Han Chinese
Received date: 2013-04-11
Revised date: 2013-09-09
Online published: 2013-10-23
High-altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that is always found among unacclimatized persons after rapid ascent to high altitude, and HAPE is caused by the interaction of genetic and environmental factors. To screen and analyze the susceptibility genes and single nucleotide polymorphisms (SNPs) of HAPE in Han Chinese, the DNA samples of 40 patients with HAPE and 33 healthy controls, who performed the reconstruction tasks from the plain region in Yushu area of Qinghai province during May of 2010 to July of 2012, were scanned by Affymetrix SNP Array 6.0 Chips in this study. Genome-wide association study (GWAS, by PLINK software) was used to screen the susceptibility genes and genetic markers, and a total of 57 SNPs were found to be significantly different between case and control groups (adjust P < 0.05). GO and Pathway enrichment analysis of 74 genes around the 57 SNPs indicated that these genes were significantly correlated with prostanoid metabolic process, arachidonic acid metabolism and nitrogen metabolism (adjust P < 0.05), which were involved in the physiopathologic mechanism of HAPE. Our studies suggest that these genetic polymorphisms and genes were associated with HAPE.
YANG Ying-Zhong WANG Ya-Ping MA Lan DU Yang GE Ri-Li . Genome-wide association study of high-altitude pulmonary edema in Han Chinese[J]. Hereditas(Beijing), 2013 , 35(11) : 1291 -1299 . DOI: 10.3724/SP.J.1005.2013.01291
[1] 高钰琪, 高文祥. 高原卫生防护手册. 北京: 人民军医出版社, 2009: 34–57.<\p>
[2] 高钰琪. 高原军事医学. 重庆: 重庆出版社, 2005: 1–4.<\p>
[3] Hotta J, Hanaoka M, Droma Y, Katsuyama Y, Ota M, Kobayashi T. Polymorphisms of renin-angiotensin system genes with high-altitude pulmonary edema in Japanese subjects. Chest, 2004, 126(3): 825–830.<\p>
[4] 中华医学会第三次全国高原医学学术讨论会推荐稿. 我国高原病命名、分型及诊断标准. 高原医学杂志, 2010, 20(1): 9–11.<\p>
[5] Smith JG, Newton-Cheh C. Genome-wide association study in humans. Methods Mol Biol, 2009, 573(2): 231–258.<\p>
[6] Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet, 2007, 81(3): 559–575.<\p>
[7] Dunnett CW. A multiple comparison procedure for com-paring several treatments with a control. J Am Stat Assoc, 1955, 50(272): 1096–1121.<\p>
[8] Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics, 2005, 21(16): 3448–3449.<\p>
[9] Jones CL, Li TS, Cowley EA. The prostaglandin E2 type 4 receptor participates in the response to acute oxidant stress in airway epithelial cells. J Pharmacol Exp Ther, 2012, 341(2): 552–563.<\p>
[10] Schoene RB, Hackett PH, Henderson WR, Sage EH, Chow M, Roach RC, Mills WJ Jr, Martin TR. High-altitude pulmonary edema. Characteristics of lung lavage fluid. JAMA, 1986, 256(1): 63–69.<\p>
[11] Zhu XF, Bouzekri N, Southam L, Cooper RS, Adeyemo A, McKenzie CA, Luke A, Chen GJ, Elston RC, Ward R. Linkage and association analysis of angiotensin I–converting enzyme (ACE)–gene polymorphisms with ACE con-centration and blood pressure. Am J Hum Genet, 2001, 68(5): 1139–1148.<\p>
[12] Gaillard S, Dellasanta P, Loutan L, Kayser B. Awareness, prevalence, medication use, and risk factors of acute mountain sickness in tourists trekking around the An-napurnas in Nepal: a 12-year follow-up. High Alt Med Biol, 2004, 5(4): 410–419.<\p>
[13] Droma Y, Hanaoka M, Ota M, Katsuyama Y, Koizumi T, Fujimoto K, Kobayashi T, Kubo K. Positive association of the endothelial nitric oxide synthase gene polymorphisms with high-altitude pulmonary edema. Circulation, 2002, 106(7): 826–830.<\p>
[14] Wang P, Koehle MS, Rupert JL. Genotype at the missense G894T polymorphism (Glu298Asp) in the NOS3 gene is associated with susceptibility to acute mountain sickness. High Alt Med Biol, 2009, 10(3): 261–267.<\p>
[15] Ahsan A, Norboo T, Baig MA, Qadar Pasha MA. Simul-taneous selection of the wild-type genotypes of the G894T and 4B/4A polymorphisms of NOS3 associate with high- altitude adaptation. Ann Hum Genet, 2005, 69(Pt 3): 260– 267.<\p>
[16] 周文婷, 胡扬, 徐飞, 邢亚卫, 衣龙彦. eNOS基因多态性与急性高山病低氧运动习服效果的关联研究. 体育科学, 2010, 30(6): 72–75.<\p>
[17] Sun YJ, Fang MW, Niu WQ, Li GP, Liu JL, Ding SQ, Xu Y, Yu GS, Dong JQ, Pan YJ, Dong WY, Wang T, Cao JW, Li XB, Wang ZX, Yu GX, Sun HC, Jia ZH, Liu J, Wang XM, Si Q, Wu QX, Zhou WY, Zhu TC, Qiu CC. Endothe-lial nitric oxide synthase gene polymorphisms associated with susceptibility to high altitude pulmonary edema in Chinese railway construction workers at Qinghai-Tibet over 4 500 meters above sea level. Chin Med Sci J, 2010, 25(4): 215–221.<\p>
[18] Luo YJ, Chen Y, Zhang Y, Zhou QQ, Gao YQ. Associa-tion of endothelial nitric oxide synthase (eNOS) G894T polymorphism with high altitude pulmonary edema sus-ceptibility: A meta-analysis. Wilderness Environ Med, 2012, 23(3): 270–274.<\p>
[19] Biljak VR, Rumora L, Cepelak I, Pancirov D, Popovi?- Grle S, Sori? J, Stjepanovi? G, Grubisi? TZ. Gamma- glutamyl-transferase and C-rea
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