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High altitude polycythemia (HAPC) refers to the long-term living in the plateau of the hypoxia environment is not accustomed to cause red blood cell hyperplasia. The pathological changes are mainly the various organs and tissue congestion, blood stasis and hypoxia damage. Although chronic hypoxia is the main cause of HAPC, the related molecular mec...
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High altitude polycythemia (HAPC) is a common chronic disease at high altitude, which is characterized by excessive erythrocytosis (females, hemoglobin ≥ 190 g/L; males, hemoglobin ≥ 210 g/L). It is the most common disease in chronic mountain sickness casued primarily by persistent arterial hypoxia and ventilatory impairment. However, the disease i...
Citations
... This may lead to a significant increase in blood viscosity, causing vessel damage and microcirculatory disturbances, vascular thrombosis, extensive organ damage, sleep disorders, and death. High oxygen affinity hemoglobin should also be considered in the assessment of patients with polycythemia [3]. Here, we report a case of cerebral thrombosis in a man in a hypercoagulable state caused by secondary polycythemia due to chronic hypoxia. ...
Background
Secondary polycythemia is considered the usual complication of chronic hypoxia. It can theoretically increase the oxygen-carrying capacity, but this adaptive trait has a deleterious effect because the blood viscosity increases, which can induce significant morbidity and mortality, such as stroke and myocardial infarction.
Case presentation
A 55-year-old man with a history of a congenitally small main pulmonary artery presented to the emergency department with sustained unsteady walking, dizziness and vertigo. Evaluation revealed elevated hemoglobin and superior posterior circulation cerebral artery thrombosis. The patient was treated with high flux inhalation of oxygen and anti-platelet aggregation.
Conclusions
The involvement of cerebral vessels has rarely been reported in chronic hypoxia cases. The present case is the first case of superior posterior circulation cerebral artery thrombosis due to chronic hypoxia in a patient with a congenitally small main pulmonary artery. This case demonstrates the importance of recognizing some chronic diseases that can lead to hypoxia and secondary polycythemia thereby leading to hypercoagulable state and subsequent thrombosis.
... High Altitude Polycythemia develops in residents in the plateau of the hypoxia environment (>3200 meters) and is mostly attributed to hypoxia but the underlying molecular mechanisms are not clear. [11,12] Some molecular mutations are likely to confer a protective mechanism and others more susceptibility. In these cases, polycythemia could be due to relative hypoxia and/or genetic predisposition (JAK-2 Mutation). ...
Objectives:
There is a higher prevalence of cerebral venous sinus thrombosis (CVST) in more recent times, owing to increased awareness, clinical diagnostic skills, and advancements in neuroimaging modalities. This study aimed to identify and characterize the geographical, clinical, and etiological profiles of patients with CVST that may be relevant to planning appropriate diagnostic and therapeutic strategies to improve functional recovery.
Methods and results:
A retrospective observational study was carried out at a tertiary care hospital between March 2014 and October 2018. The demographics and clinical profile of the hospitalized patients were extracted from the Medical Record Division. Choropleth maps were created to present the geographic distribution of the patients with CVST admitted to our hospital. A total of 145 patients with CVST were included in the study. Etiological factors revealed striking abnormalities in red blood cells counts and serum homocysteine. Analyzing the geographical distribution of the patients with CVST showed most of the patients hailed from Central Karnataka Plateau 106 (73%). Polycythemia was most commonly seen in patients residing in the Central Karnataka Plateau 21 (62%).
Conclusion:
It is inferred that large scale community-based studies to identify a genetic abnormality like a mutant erythropoietin gene should be undertaken to plan effective diagnostic, therapeutic, and preventive measures.
... Recent studies revealed that HAPC in Tibetans or Han is associated with several gene polymorphisms, such as phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta gene (PIK3CD), collagen type IV a3 chain gene (COL4A3), integrin subunit alpha six gene (ITGA6), erb-b2 receptor tyrosine kinase four gene (ERBB4), EPH receptor A2 gene (EPHA2), angiotensinogen gene (AGT), and endothelial PAS domain protein one gene (EPAS1) [7][8][9][10][11] EPHA2 can disturb erythropoiesis by regulating EPO production, and EPAS1 contributes to genetic adaptation to high altitudes and the particular trait of the low Hb concentrations, conditions frequently observed among Tibetans [9,12]. HAPC was found to lead to morphological changes and pathological damage to the gastric mucosa of patients. ...
... Recent studies revealed that HAPC in Tibetans or Han is associated with several gene polymorphisms, such as phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta gene (PIK3CD), collagen type IV a3 chain gene (COL4A3), integrin subunit alpha six gene (ITGA6), erb-b2 receptor tyrosine kinase four gene (ERBB4), EPH receptor A2 gene (EPHA2), angiotensinogen gene (AGT), and endothelial PAS domain protein one gene (EPAS1) [7][8][9][10][11] EPHA2 can disturb erythropoiesis by regulating EPO production, and EPAS1 contributes to genetic adaptation to high altitudes and the particular trait of the low Hb concentrations, conditions frequently observed among Tibetans [9,12]. HAPC was found to lead to morphological changes and pathological damage to the gastric mucosa of patients. ...
High-altitude polycythemia (HAPC) is characterized by excessive proliferation of erythrocytes, resulting from the hypobaric hypoxia condition in high altitude. The genetic variants and molecular mechanisms of HAPC remain unclear in highlanders. We recruited 141 Tibetan dwellers, including 70 HAPC patients and 71 healthy controls, to detect the possible genetic variants associated with the disease; and performed targeted sequencing on 529 genes associated with the oxygen metabolism and erythrocyte regulation, utilized unconditional logistic regression analysis and GO (gene ontology) analysis to investigate the genetic variations of HAPC. We identified 12 single nucleotide variants, harbored in 12 genes, associated with the risk of HAPC (4.7 ≤ odd ratios ≤ 13.6; 7.6E - 08 ≤ p-value ≤ 1E - 04). The pathway enrichment study of these genes indicated the three pathways, the PI3K-AKT pathway, JAK-STAT pathway, and HIF-1 pathway, are essential, which p-values as 3.70E - 08, 1.28 E - 07, and 3.98 E - 06, respectively. We are hopeful that our results will provide a reference for the etiology research of HAPC. However, additional genetic risk factors and functional investigations are necessary to confirm our results further.
Supplementary information:
The online version contains supplementary material available at 10.1007/s12288-021-01474-1.
... This genetic diversity can also be a source of differences in genetic risk for particular ailments between different populations. For example, variant rs2478523 in the AGT gene shows an increase in the risk of high altitude polycythemia (HAPC) in the Tibetan population while in the Han population, rs699, rs4762 and rs5051 are associated with reduced HAPC susceptibility [10]. Also, in the USA population, a minor allele rs5065 in NPPA was identified as a marker of increased cardiovascular risk [11], and in the North Indian population, rs1042571 in POMC was shown to increase the risk of obesity [12]. ...
Background:
Publicly available genome data provides valuable information on the genetic variation patterns across different modern human populations. Neuropeptide genes are crucial to the nervous, immune, endocrine system, and physiological homeostasis as they play an essential role in communicating information in neuronal functions. It remains unclear how evolutionary forces, such as natural selection and random genetic drift, have affected neuropeptide genes among human populations. To date, there are over 100 known human neuropeptides from the over 1000 predicted peptides encoded in the genome. The purpose of this study is to analyze and explore the genetic variation in continental human populations across all known neuropeptide genes by examining highly differentiated SNPs between African and non-African populations.
Results:
We identified a total of 644,225 SNPs in 131 neuropeptide genes in 6 worldwide population groups from a public database. Of these, 5163 SNPs that had ΔDAF |(African - non-African)| ≥ 0.20 were identified and fully annotated. A total of 20 outlier SNPs that included 19 missense SNPs with a moderate impact and one stop lost SNP with high impact, were identified in 16 neuropeptide genes. Our results indicate that an overall strong population differentiation was observed in the non-African populations that had a higher derived allele frequency for 15/20 of those SNPs. Highly differentiated SNPs in four genes were particularly striking: NPPA (rs5065) with high impact stop lost variant; CHGB (rs6085324, rs236150, rs236152, rs742710 and rs742711) with multiple moderate impact missense variants; IGF2 (rs10770125) and INS (rs3842753) with moderate impact missense variants that are in linkage disequilibrium. Phenotype and disease associations of these differentiated SNPs indicated their association with hypertension and diabetes and highlighted the pleiotropic effects of these neuropeptides and their role in maintaining physiological homeostasis in humans.
Conclusions:
We compiled a list of 131 human neuropeptide genes from multiple databases and literature survey. We detect significant population differentiation in the derived allele frequencies of variants in several neuropeptide genes in African and non-African populations. The results highlights SNPs in these genes that may also contribute to population disparities in prevalence of diseases such as hypertension and diabetes.
... We selected two polymorphisms in the AGT gene, i.e., rs699 (M235T in exon 2) and rs5050 (A-20C in the promoter region), for detection. The selection of the two functional polymorphisms was based on a thorough evaluation of polymorphisms associated with vasculopathy [22,[25][26][27]. Genomic DNA was extracted from all KD cases and controls blood using the TIANamp Blood DNA Kit (Qiagen, Dusseldorf, Germany). ...
... Ang II can stimulate excessive hypertrophy, the proliferation of vascular smooth muscle cells, and increased platelet adhesion, causing vascular injury, such as atherosclerosis and thrombosis. AGT gene polymorphisms have been found to be related to vascular injuryrelated diseases by researchers in Russia, India, Australia, and China [22,25,26,32]. However, few reports exist on the relationship between AGT gene polymorphisms and the risk of CAA with KD, and the number of cases in these studies is insufficient [7]. ...
Background:
Kawasaki disease (KD) is an acute vasculitis disease that commonly causes acquired heart disease in children. Coronary artery aneurysm (CAA) is a major complication of KD. However, the pathogenesis of KD remains unclear. The results of a genome-wide association study (GWAS) showed that two functional single-nucleotide polymorphisms (SNPs; rs699A>G and rs5050T>G) in the angiotensinogen (AGT) gene were related to cardiovascular disease susceptibility. The purpose of our study was to estimate the relationship between the two GWAS-identified AGT gene polymorphisms and the risk of CAA in Southern Chinese children with KD.
Methods:
We genotyped the two AGT gene polymorphisms (rs699A>G and rs5050T>G) in 760 KD cases and 972 healthy controls. We used the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the degree of the associations.
Results:
These two AGT gene polymorphisms were not associated with a risk of KD relative to the controls, but after adjusting for sex and age, the carriers of the rs5050G allele with TG/GG vs TT had an adjusted OR = 1.56, 95% CI = 1.01-2.41, and P = 0.044 relative to the carriers of the rs5050TT genotype. The susceptibility to CAA was more predominant in KD patients younger than 12 months old.
Conclusions:
Our results indicate that the AGT gene polymorphism rs5050T>G may increase the risk of CAA in children with KD, especially those who are younger than 12 months. These results need to be verified by a validation study with a larger sample size.
... Recently, significant progress has been made in the study of the genetic basis of HAPC in Tibetans and Han, and some studies have confirmed that many genes are associated with HAPC. Namely, integrin subunit alpha 6 (ITGA6), erb-b2 receptor tyrosine kinase 4 (ERBB4), EPH receptor A2 (EPHA2), angiotensinogen (AGT), and endothelial PAS domain protein 1 (EPAS1) have been reported to play important roles in HAPC in Tibetans and Han [23][24][25][26]. Of these genes, EPHA2 can affect erythrocyte production by regulating EPO production and EPAS1 has been implicated as making the greatest contribution to genetic adaptation to high altitude and to the low Hb concentrations observed in the Tibetan population [18,21]. ...
Background
High-altitude polycythemia (HAPC) is a chronic high-altitude disease that can lead to an increase in the production of red blood cells in the people who live in the plateau, a hypoxia environment, for a long time. The most frequent symptoms of HAPC include headache, dizziness, breathlessness, sleep disorders, and dilation of veins. Although chronic hypoxia is the main cause of HAPC, the fundamental pathophysiologic process and related molecular mechanisms responsible for its development remain largely unclear yet.
Aim/methods
This study aimed to explore the related hereditary factors of HAPC in the Chinese Han and Tibetan populations. A total of 140 patients (70 Han and 70 Tibetan) with HAPC and 60 healthy control subjects (30 Han and 30 Tibetan) were recruited for a case-control association study. To explore the genetic basis of HAPC, we investigated the association between HAPC and both phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta gene (PIK3CD) and collagen type IV α3 chain gene (COL4A3) in Chinese Han and Tibetan populations.
Results/conclusion
Using the unconditional logistic regression analysis and the false discovery rate (FDR) calculation, we found that eight SNPs in PIK3CD and one SNP in COL4A3 were associated with HAPC in the Tibetan population. However, in the Han population, we did not find any significant association. Our study suggested that polymorphisms in the PIK3CD and COL4A3 were correlated with susceptibility to HAPC in the Tibetan population.
Background:
Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor.
Research design and methods:
This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models.
Results:
In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13,972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20).
Conclusions:
The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.
Angiotensinogen (AGT) is one of the most significant enzymes of the renin-angiotensin-aldosterone system (RAAS) which is involved in the regulation and maintenance of blood pressure. AGT is involved in the production of angiotensin I which is then converted into angiotensin II that leads to renal homeostasis. However, various genetic polymorphisms in AGT have been discovered in recent times which have shown an association with various diseases. Genetic polymorphism increases the level of circulating AGT in blood which exaggerates the effects produced by AGT. The associated diseases occur due to various effects produced by increased AGT levels. Several cardiovascular diseases including myocardial infarction, coronary heart disease, heart failure, hypertrophy, etc. are associated with AGT polymorphism. Other diseases such as depression, obesity, diabetic nephropathy, pre-eclampsia, and liver injury are also associated with some variants of AGT gene. The most common variants of AGT polymorphism are M235T and T174M. The two variants are associated with many diseases. Some other variants such as G-217A, A-6G, A-20C and G-152A, are also present but they are not as significant as that of M235T and T174M variants. These variants increase the level of circulating AGT and are associated with prevalence of different diseases. These diseases occur through various pathological pathways, but the initial reason remains the same, i.e., increased level of AGT in the blood. In this article, we have majorly focused on how genetic polymorphism of different variants of AGT gene is associated with the prevalence of different diseases.
In high-altitude environments, the prevalence of high-altitude polycythemia (HAPC) ranges between 5 and 18 percent. However, there is currently no effective treatment for this condition. Therefore, disease prevention has emerged as a critical strategy against this disease. Here, we looked into the microarray profiles of GSE135109 and GSE29977, linked to either short- or long-term exposure to the Qinghai Tibet Plateau (QTP). The results revealed inhibition in the adaptive immune response during 30 days of exposure to QTP. Following a gene set enrichment analysis (GSEA) discovered that genes associated with HAPC were enriched in Cluster1, which showed a dramatic upregulation on the third day after arriving at the QTP. We then used GeneLogit to construct a logistic prediction model, which allowed us to identify 50 genes that classify HAPC patients. In these genes, LRRC18 and HCAR3 were also significantly altered following early QTP exposure, suggesting that they may serve as hub genes for HAPC development. The in-depth study of a combination of the datasets of transcriptomic changes during exposure to a high altitude and whether diseases occur after long-term exposure in Hans can give us some inspiration about genes associated with HAPC development during adaption to high altitudes.
