ArticleEuropean journal of epidemiology2008
Synergistic effect of the genetic polymorphisms of the renin-angiotensin-aldosterone system on high-altitude pulmonary edema: a study from Qinghai-Tibet altitude.
Article in European journal of epidemiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- G Protein-Coupled Receptor in High-Altitude Diseases: Mechanistic Insights and Therapeutic Opportunities.MedComm · 2026Review
- Altitude hypoxia and hypoxemia: pathogenesis and management.Signal transduction and targeted therapy · 2026Review
- Association of variants m.T16172C and m.T16519C in whole mtDNA sequences with high altitude pulmonary edema in Han Chinese lowlanders.BMC pulmonary medicine · 2022Article
- Comparative transcriptomic and proteomic analyses provide insights into functional genes for hypoxic adaptation in embryos of Tibetan chickens.Scientific reports · 2020Article
- Interindividual Variation in Cardiorespiratory Fitness: A Candidate Gene Study in Han Chinese People.Genes · 2020Article
- SNPs, linkage disequilibrium, and chronic mountain sickness in Tibetan Chinese.Hypoxia (Auckland, N.Z.) · 2017Article
- Angiotensin II receptor 1 gene variants are associated with high-altitude pulmonary edema risk.Oncotarget · 2016Article
- Association of nineteen polymorphisms from seven DNA repair genes and the risk for bladder cancer in Gansu province of China.Oncotarget · 2016Article
- Biomarkers of hypoxia, endothelial and circulatory dysfunction among climbers in Nepal with AMS and HAPE: a prospective case-control study.Journal of travel medicine · 2016Article
- Association between genetic polymorphisms of ACE & eNOS and diabetic nephropathy.Molecular biology reports · 2015Article
- Association ofBiomedical reports · 2014Article
- Tag polymorphisms of solute carrier family 12 member 3 gene modify the risk of hypertension in northeastern Han Chinese.Journal of human hypertension · 2014Article
- Interactive contribution of serine/threonine kinase 39 gene multiple polymorphisms to hypertension among northeastern Han Chinese.Scientific reports · 2014Article
- Synergistic association between two alcohol metabolism relevant genes and coronary artery disease among Chinese hypertensive patients.PloS one · 2014Article
- The contributory role of angiotensin receptor-like 1 gene multiple polymorphisms in hypertension among northeastern Han Chinese.PloS one · 2014Article
- Article
- Gene-gene interactions in renin-angiotensin-aldosterone system contributes to end-stage renal disease susceptibility in a Han Chinese population.TheScientificWorldJournal · 2014Article
- Association study of ACE polymorphisms and systemic lupus erythematosus in Northern Chinese Han population.Molecular biology reports · 2012Article
- Hypoxic pulmonary vasoconstriction.Physiological reviews · 2012Review
- The ACE gene and human performance: 12 years on.Sports medicine (Auckland, N.Z.) · 2011Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathogenesis of high-altitude pulmonary edema (HAPE) has been at least partially attributed to the local dysregulation of the renin-angiotensin-aldosterone system (RAAS) cascade. To address this issue, we conducted the largest nested case-control study to-date to explore the association between variations in RAAS genes and HAPE in Chinese population. We recruited 140 HAPE patients and 144 controls during the construction of Qinghai-Tibet railway and genotyped 10 gene polymorphisms evenly interspersed in 5 RAAS candidate genes. The data were analyzed by haplotype and multifactor dimensionality reduction (MDR). The single-locus analysis showed that CYP11B2 C-344T and K173R and ACE A-240T polymorphisms were significantly associated with HAPE after Bonferroni correction (P<0.005). The linkage analysis constructed a linkage block including C-344T and K173R polymorphisms in complete linkage disequilibrium with each other, while occurred with significantly different frequencies between HAPE and control groups. The gene-gene interaction analysis found the overall best model including ACE A-240T and A2350G and CYP11B2 C-344T polymorphisms with strong synergistic effect. This model had a maximum testing accuracy of 68.61% and a maximum cross validation consistency of 9 out of 10 (P=0.004). The homozygous genotype combination of -240AA, 2350GG and -344TT conferred high genetic susceptibility to HAPE, which was further strengthened by haplotype analysis. Our results add evidence for synergistic effect of RAAS gene polymorphisms on HAPE susceptibility. Moreover, we proposed a promising data-mining analytical approach (MDR) for detecting and characterizing gene-gene interactions.
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