Statistical analyses of the genotype frequencies of the SNPs revealed significant differences in the ACE (rs4309), EGLN1 (rs480902), SP-A2 (rs1965708), HSP70 (rs1008438), PAI-1 (rs1799889), and NOS (rs199983) expressions between the HAPE and healthy control groups (P < 0.05); therefore, these SNP loci were believed to indicate HAPE susceptibility.
These findings demonstrate a possible association of the I/D polymorphism of the ACE gene with the development of HAPE, with D/D being the at-risk genotype.
To assess associations between genetic variants in the ACE and NOS3 genes and HAPE risk, 27 HAPE patients and 108 matched controls were genotyped and analyzed.
We aimed to assess the association between the angiotensin-converting enzyme (ACE) I/D polymorphism and HAPE via a meta-analysis of published and unpublished data.
The single-locus analysis showed that CYP11B2 C-344T and K173R and ACEA-240T polymorphisms were significantly associated with HAPE after Bonferroni correction (P<0.005).
Meta-analysis showed overall association of NOS3G894T SNP with HAPE risk under the allele contrast and dominant genetic models, which remained significant for Asians.
Several laboratories, including ours, have shown that variants in NOS3 (the gene encoding eNOS) are overrepresented in individuals with altitude-related illnesses such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS), suggesting that NOS3 genotypes contribute to altitude tolerance.
Previous genetic association studies in high-risk subjects have suggested that polymorphisms in the gene encoding endothelial nitric oxide synthase (eNOS) may be associated with susceptibility to high altitude pulmonary edema (HAPE).
In the present study, we investigated G894T, 27-base-pair 4b/4a (variable number of tandem repeat), -922A/G, and -786T/C polymorphisms of NOS3, individually or in combination, for an association with HAPE.
Recent studies have shown a possible association between HAPE and polymorphisms in genes of the renin-angiotensin-aldosterone system (RAAS), which play a key role in sensitivity of an individual toward HAPE.
The genes associated with HAPE include those in the renin-angiotensin-aldosterone system pathway, the nitric oxide pathway and the hypoxia-inducible factor pathway.
Association of polymorphisms in angiotensin and aldosterone synthase genes of the renin-angiotensin-aldosterone system with high-altitude pulmonary edema.