Angiotensin II receptor 1 gene variants are associated with high-altitude pulmonary edema risk

Jin, Tianbo; Ren, Yichao; Zhu, Xikai; Li, Xun; Ouyang, Yongri; He, Na; Zhang, Zhiying; Yuan, Zhaonian; Kang, Longli; Yuan, Dongya

doi:10.18632/oncotarget.12489

Cited by 8 publications

(10 citation statements)

References 24 publications

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“…Disturbance of the RAAS is attributed, in part, to genetic variants in at least five critical genes namely REN, AGT , ACE, AGTR1 , and CYP11B2 . 20 , 49 – 53 Of these, the major genetic variants that have been associated with HAPE are rs4762 (Thr207Met) and rs699 (Met268Thr) of AGT , 53 , 54 the insertion/deletion (indel) alleles (I/D, 287bp alu repeat sequence), rs8066114 and rs4461142 of ACE , 20 , 50 , 51 , 53 , 55 rs275651 and rs275652 of AGTR1 , 56 and –344T/C and intron 2 conversion of CYP11B2 ( Fig. 1 and Table 1 ).…”

Section: Renin–angiotensin–aldosterone System-mediated Allele-specifimentioning

confidence: 99%

Vascular homeostasis at high‐altitude: role of genetic variants and transcription factors

et al. 2020

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total number of manuscript pages -41 • total number of figures -4 • word count for the body of the text -7834 • type of contribution -review article AbstractHigh-altitude pulmonary edema (HAPE) occurs most frequently in non-acclimatized low landers on exposure to altitude ≥2500m. HAPE is a complex condition that involves perturbation of signaling pathways in vasoconstrictors, vasodilators, anti-diuretics and vascular growth factors. Genetic variations are instrumental in regulating these pathways and evidence is accumulating for a role of epigenetic modification in hypoxic responses. This review focuses on the crosstalk between HAPE-associated genetic variants and transcription factors, comparing high-altitude adapted and HAPE-afflicted subjects. This approach might ultimately yield biomarker information both to understand and to design therapies for high altitude adaptation.Evolution and physiological adaptation have permitted survival at the highest topographically elevated regions of the world. [1][2][3][4][5] Reduced air pressure at high-altitude decreases the partial pressure of inspired oxygen, affecting lungs, brain, heart and blood and can lead to a spectrum of high-altitude disorders including high-altitude pulmonary edema (HAPE), acute mountain sickness (AMS) and high-altitude cerebral edema (HACE). 6,7 This review focuses on HAPE. HAPE is a consequence of hypoxic pulmonary vasoconstriction leading to increased pulmonary arterial pressure and capillary stress failure. 8-11 HAPE victims have lower arterial oxygen saturation (SaO2) and higher heart rate, pulmonary vascular resistance and pulmonary vascular resistance index 12,13 than do unaffected sojourners to altitude. Clinically HAPE is characterized by dyspnoea, elevated body temperature, pink frothy sputum, tachypnoea, tachycardia, persistent cough and cyanosis. [14][15][16][17] Chest X-rays and CT scans show increased lung vascular markings and patchy shadows. 18,19 There have been great strides in understanding the clinical and physiological mechanisms of HAPE that has led to the discovery of successful treatments. Information on genetic contributions to this disorder has also grown rapidly over the last decade, partly to the development and implementation of newer genetic techniques. Candidate-gene approaches, advanced techniques such as Next-GenerationSequencing and Genome-Wide Association Studies have led to association of multiple genetic variants with high-altitude adaptation or maladaptation. [20][21][22][23][24][25][26] The majority of these genes belong to multiple, frequently related pathways. These include the renin-angiotensin aldosterone system, apelin signaling, nitric oxide signaling, and hypoxia induced signaling.These pathways regulate vasoactive molecules including angiotensin II, apelin, nitric oxide, aldosterone, and beta-adrenergics. [27][28][29][30][31] In addition to genetic variation, epigenetics plays prominent role in HAPE and other diseases. [32][33][34][35] DNA methylation, acetylation, histone modifications/chromatin rem...

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Section: Renin–angiotensin–aldosterone System-mediated Allele-specifimentioning

confidence: 99%

Vascular homeostasis at high‐altitude: role of genetic variants and transcription factors

et al. 2020

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“…This gene encodes the angiotensin II receptor 1 (AT 1 R), and polymorphisms in AGTR1 have been suggested to be involved in the physiological response to hypoxia [62]. AT 1 R is broadly expressed in different tissues and mediates most of the classical actions of angiotensin II, including vasoconstriction and vascular smooth muscle cell proliferation [63]. Thus, under hypoxic conditions, angiotensin II engages AT 1 R to modulate the pulmonary vasoconstrictive response [64].…”

Section: Discussionmentioning

confidence: 99%

Interindividual Variation in Cardiorespiratory Fitness: A Candidate Gene Study in Han Chinese People

Gaowa

Coso

et al. 2020

Genes

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Cardiorespiratory fitness, as assessed through peak oxygen uptake (VO2peak), is a powerful health indicator. We aimed to evaluate the influence of several candidate causal genetic variants on VO2peak level in untrained Han Chinese people. A total of 1009 participants (566 women; age [mean ± SD] 40 ± 14 years, VO2peak 29.9 ± 7.1 mL/kg/min) performed a maximal incremental cycling test for VO2peak determination. Genomic DNA was extracted from peripheral whole blood, and genotyping analysis was performed on 125 gene variants. Using age, sex, and body mass as covariates, and setting a stringent threshold p-value of 0.0004, only one single nucleotide polymorphism (SNP), located in the gene encoding angiotensin-converting enzyme (rs4295), was associated with VO2peak (β = 0.87; p < 2.9 × 10−4). Stepwise multiple regression analysis identified a panel of three SNPs (rs4295 = 1.1%, angiotensin II receptor type 1 rs275652 = 0.6%, and myostatin rs7570532 = 0.5%) that together accounted for 2.2% (p = 0.0007) of the interindividual variance in VO2peak. Participants carrying six ‘favorable’ alleles had a higher VO2peak (32.3 ± 8.1 mL/kg/min) than those carrying only one favorable allele (24.6 ± 5.2 mL/kg/min, p < 0.0001). In summary, VO2peak at the pre-trained state is partly influenced by several polymorphic variations in candidate genes, but they represent a minor portion of the variance.

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“…heart rate and respiratory rate) required for the diagnosis of HAPE so that their results could be compared with other genetic studies carried out on HAPE. 3,4 He et al 1 reported that none of the subjects of control group (who had same ascent rate and altitude as achieved by the HAPE cases) developed signs and symptoms of HAPE within 7 days of exposure to high altitude. The basis of choosing a '7-day' period of observation for the control group is not clear because HAPE is known to occur mostly 2-4 days after reaching an altitude of 3000 m or more.…”

Section: Risk Of High Altitude Pulmonary Edema and Telomere Lengthmentioning

confidence: 99%

“…It would have been appropriate for He et al to have also included other important parameters (e.g. heart rate and respiratory rate) required for the diagnosis of HAPE so that their results could be compared with other genetic studies carried out on HAPE . He et al reported that none of the subjects of control group (who had same ascent rate and altitude as achieved by the HAPE cases) developed signs and symptoms of HAPE within 7 days of exposure to high altitude.…”

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confidence: 99%

Risk of high altitude pulmonary edema and telomere length

Sikri

Bhattachar²

2017

The Journal of Gene Medicine

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Angiotensin II receptor 1 gene variants are associated with high-altitude pulmonary edema risk

Cited by 8 publications

References 24 publications

Vascular homeostasis at high‐altitude: role of genetic variants and transcription factors

Vascular homeostasis at high‐altitude: role of genetic variants and transcription factors

Interindividual Variation in Cardiorespiratory Fitness: A Candidate Gene Study in Han Chinese People

Risk of high altitude pulmonary edema and telomere length

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