angiotensinogen and Altitude-Sickness

Altitude illness refers to a group of environmentally mediated pathophysiologies. Many people will suffer acute mountain sickness shortly after rapidly ascending to a moderately hypoxic environment, and an unfortunate few will develop potentially fatal conditions such as high altitude pulmonary edema or high altitude cerebral edema. Some individuals seem to be predisposed to developing altitude illness, suggesting an innate contribution to susceptibility. The implication that there are altitude-sensitive and altitude-tolerant individuals has stimulated much research into the contribution of a genetic background to the efficacy of altitude acclimatization. Although the effect of altitude attained and rate of ascent on the etiology of altitude illness is well known, there are only tantalizing, but rapidly accumulating, clues to the genes that may be involved. In 2006, we reviewed what was then known about the genetics of altitude illness. This article updates that review and attempts to tabulate all the available genetic data pertaining to these conditions. To date, 58 genes have been investigated for a role in altitude illness. Of these, 17 have shown some association with the susceptibility to, or the severity of, these conditions, although in many cases the effect size is small or variable. Caution is recommended when evaluating the genes for which no association was detected, because a number of the investigations reviewed in this article were insufficiently powered to detect small effects. No study has demonstrated a clear-cut altitude illness gene, but the accumulating data are consistent with a polygenic condition with a strong environmental component. The genes that have shown an association affect a variety of biological pathways, suggesting that either multiple systems are involved in altitude pathophysiology or that gene-gene interactions play a role. Although numerous studies have been performed to investigate specific genes, few have looked for evidence of heritability or familial transmission, or for epidemiological patterns that would be consistent with genetically influenced conditions. Future trends, such as genome-wide association studies and epigenetic analysis, should lead to enhanced understanding of the complex interactions within the genome and between the genome and hypoxic environments that contribute to an individual's capacity to acclimatize rapidly and effectively to altitude.

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); ABO Blood-Group System; Acclimatization; Alleles; Altitude Sickness; Angiotensin-Converting Enzyme 2; Angiotensinogen; Apolipoproteins B; Cyclin-Dependent Kinase Inhibitor p27; Cytochrome P-450 CYP11B2; Endothelins; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glutathione Transferase; Heat-Shock Proteins; Heterotrimeric GTP-Binding Proteins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intracellular Signaling Peptides and Proteins; Mountaineering; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Receptor, Bradykinin B2; Receptors, Adrenergic, beta-2; Serotonin Plasma Membrane Transport Proteins; Vascular Endothelial Growth Factor A; Von Hippel-Lindau Tumor Suppressor Protein

To research the effects of gene polymorphisms of AGT at G-217A and T174M loci on incidence and the hypoxia acclimation to acute mountain sickness (AMS).. In step 1 the hypoxic exposure, for the G-217A locus in AGT, there was no significant difference between GG and GA+AA gene tester. While in step 2 the hypoxic exposure, the SpO. The G-217A may be the genetics sign of hypoxia acclimation. There is no obvious rel-evancy between the T174M polymorphism and the occurrence of AMS/hypoxia acclimation.

Topics: Acclimatization; Altitude Sickness; Angiotensinogen; Blood Pressure Monitoring, Ambulatory; Heart Rate; Humans; Hypoxia; Polymorphism, Genetic

Acute (AMS) and chronic (CMS) mountain sicknesses are illnesses that occur among humans visiting or inhabiting high-altitude environments, respectively. Some individuals are genetically less fit than others when stressed by an extreme high-altitude environment. Seven blood physiological parameters and five genetic polymorphisms were studied in Han patients with AMS and Tibetan patients with CMS.. We compared 98 AMS patients with 60 Han controls as well as 50 CMS patients with 36 Tibetan controls. The genetic loci studied are ACE I/D (rs4340), AGT M235T (rs699), AGTR1 A1166C (rs5186), GNB3 A(-350)G (rs2071057) and APOB A/G (rs693).. All physiological parameters (RBC, HCT, Hb, SaO(2), HR, and BPs/d) studied significantly changed in the CMS patients while SaO(2) and HR changed in the AMS Han patients compared to their controls. The ACE D and AGT 235M alleles were found to be significantly associated with AMS and CMS, respectively, while a significantly high incidence of the G-protein (GNB3) (-350)A allele was found in the AMS patients. ACE (I/D) was significantly associated with HR in CMS patients while the AGT M235T was significantly associated with SaO(2) and BPs/d in AMS patients. APOB A/G was significantly associated with BPs/d in AMS and HR in CMS patients.. AMS and CMS share very similar genetic results for the ACE I/D and AGT M235T polymorphisms indicating that these mutations have an effect on both illnesses.

Topics: Acute Disease; Altitude; Altitude Sickness; Angiotensinogen; China; Chronic Disease; Genome-Wide Association Study; Geography; Hematologic Tests; Humans; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Tibet