title: Endothelial 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.
abstract: 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 Pü0.0001). 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 Pü0.001).
  
  
  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.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Yu-jing
authors.forename: Fang
authors.initials: F
authors.lastname: Ming-wu
authors.forename: Niu
authors.initials: N
authors.lastname: Wen-quan
authors.forename: Li
authors.initials: L
authors.lastname: Guang-ping
authors.forename: Liu
authors.initials: L
authors.lastname: Jing-liang
authors.forename: Ding
authors.initials: D
authors.lastname: Shou-quan
authors.forename: Xu
authors.initials: X
authors.lastname: Ying
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo-shu
authors.forename: Dong
authors.initials: D
authors.lastname: Jian-qun
authors.forename: Pan
authors.initials: P
authors.lastname: Yun-jun
authors.forename: Dong
authors.initials: D
authors.lastname: Wei-ya
authors.forename: Wang
authors.initials: W
authors.lastname: Tian
authors.forename: Cao
authors.initials: C
authors.lastname: Jing-wen
authors.forename: Li
authors.initials: L
authors.lastname: Xiao-bo
authors.forename: Wang
authors.initials: W
authors.lastname: Zhong-xiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Guang-Xue
authors.forename: Sun
authors.initials: S
authors.lastname: Hui-cheng
authors.forename: Jia
authors.initials: J
authors.lastname: Zhong-hou
authors.forename: Liu
authors.initials: L
authors.lastname: Jun
authors.forename: Wang
authors.initials: W
authors.lastname: Xiao-ming
authors.forename: Si
authors.initials: S
authors.lastname: Qin
authors.forename: Wu
authors.initials: W
authors.lastname: Qi-xia
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wen-yu
authors.forename: Zhu
authors.initials: Z
authors.lastname: Tong-chun
authors.forename: Qiu
authors.initials: Q
authors.lastname: Chang-chun
mesh_terms: D000293:Adolescent; D000328:Adult; D000531:Altitude; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009784:Occupational Diseases / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011654:Pulmonary Edema / Q000201:enzymology / Q000235:genetics*; D018609:Tibet; D055815:Young Adult
chemical_list: D017931:DNA Primers; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III