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.

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.

Associations between RAS Gene polymorphisms, environmental factors and hypertension in Mongolian people.

OBJECTIVE: To explore the association between RAS system genes (AGT, ACE and AT(1)R) polymorphisms, environmental factors and hypertension in Mongolian people. METHODS: On the basis of cross-sectional study, a case-control study with 299 hypertensives and 281 nomotensives was conducted, and the conditions of environmental factors were acquired by questionnaire. Serum lipid and insulin were detected by using biochemical experiments. Six single nucleotide polymorphisms of RAS system were genotyped by polymerase chain reaction/restriction fragment length polymorphism and polymerase chain reaction/single strand conformation polymorphism. RESULTS: Overweight or obesity, high serum TG and insulin resistance were risk factors of hypertension by single factor analysis. All the RAS genotype distributions were compatible with Hardy-Weinberg expectations. There were no significant differences to be found between cases and controls for genotype frequencies or allele frequencies of the six polymorphisms of RAS system, except in men group, OR value of men carried ACE ID+DD genotype vs. men carried II genotype was 2.20 (95%CI 1.21-4.02), and OR of people who carried both ACE ID (or DD) and AGT M235T MT (or MM) vs. people with both ACE ID (or DD) and AGT M235T TT was 1.59 (95%CI 1.06-2.38). CONCLUSIONS: Overweight or obesity, dyslipidemia and insulin resistance were risk factors of hypertension in Mongolian people. ACE gene ID+DD genotype was the risk factor of hypertension in men group. People who carried both ACE ID (or DD) and AGT M235T MT (or MM) had more risk to have hypertension.