Endothelial Nitric Oxide Synthase Gene Polymorphisms Associated with Susceptibility to High Altitude Pulmonary Edema in Chinese Railway Construction Workers at Qinghai-Tibet over 4500 Meters above Sea Level  

作　　者：Yu-jing Sun Ming-wu Fang Wen-quan Niu Guang-ping Li Jing-liang Liu Shou-quan Ding Ying Xu Guo-shu Yu Jian-qun Dong Yun-jun Pan Guang-xue Yu Hui-cheng Sun Zhong-hou Jia Jun Liu Xiao-ming Wang Qin Si Qi-xia Wu Wen-yu Zhou Tong-chun Zhu Chang-chun Qiu 

机构地区：[1]National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Beijing 100005, China [2]Hospital of China Railway Construction Corporation, Beijing 100039, China

出　　处：《Chinese Medical Sciences Journal》2010年第4期215-221,共7页中国医学科学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China (30393130, 30470651);National Basic Research Program of China (973 Program) (2006BAI19B07, 2006CB504103);National Key Laboratory Specific Fund (2060204)

摘　　要：Objective To examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level. Methods A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing. Results The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both P<0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both P<0.001). Conclusions Two haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.

关 键 词：high altitude pulmonary edema nitric oxide synthase gene polymorphism HAPLOTYPE 

分 类 号：Q346.5[生物学—遗传学] F426.9[经济管理—产业经济]