SENP1, but not fetal hemoglobin, differentiates Andean highlanders with chronic mountain sickness from healthy individuals among Andean highlanders

Hsieh, Matthew M.; Callacondo, David; Rojas-Camayo, Jose; Quesada-Olarte, José; Wang, Xunde; Uchida, Naoya; Marić, Irina; Remaley, Alan T.; León‐Velarde, Fabiola; Villafuerte, Francisco C.; Tisdale, John F.

doi:10.1016/j.exphem.2016.02.010

Cited by 17 publications

(11 citation statements)

References 43 publications

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“…Mean sleep SpO 2 was also associated with CMS score in men only ( Figure 4E). The severe desaturation events during sleep may explain why showed serum Epo during sleep was significantly higher in men with CMS, in contrast to findings of similar Epo levels in CMS and healthy male participants during the day (León-Velarde et al, 1991;Villafuerte et al, 2014;Hsieh et al, 2016). also showed that mean sleep SpO 2 , total sleep time below 80% SpO 2 , and the Epo-to-soluble Epo receptor ratio (an Epo availability index) were significant predictors of Hct in men.…”

Section: Sleepmentioning

confidence: 87%

Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women

et al. 2020

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Andean highlanders are challenged by chronic hypoxia and many exhibit elevated hematocrit (Hct) and blunted ventilation compared to other high-altitude populations. While many Andeans develop Chronic Mountain Sickness (CMS) and excessive erythrocytosis, Hct varies markedly within Andean men and women and may be driven by individual differences in ventilatory control and/or sleep events which exacerbate hypoxemia. To test this hypothesis, we quantified relationships between resting ventilation and ventilatory chemoreflexes, sleep desaturation, breathing disturbance, and Hct in Andean men and women. Ventilatory measures were made in 109 individuals (n = 63 men; n = 46 women), and sleep measures in 45 of these participants (n = 22 men; n = 23 women). In both men and women, high Hct was associated with low daytime SpO 2 (p < 0.001 and p < 0.002, respectively) and decreased sleep SpO 2 (mean, nadir, and time <80%; all p < 0.02). In men, high Hct was also associated with increased end-tidal P CO2 (p < 0.009). While ventilatory responses to hypoxia and hypercapnia did not predict Hct, decreased hypoxic ventilatory responses were associated with lower daytime SpO 2 in men (p < 0.01) and women (p < 0.009) and with lower nadir sleep SpO 2 in women (p < 0.02). Decreased ventilatory responses to CO 2 were associated with more time below 80% SpO 2 during sleep in men (p < 0.05). The obstructive apnea index and apnea-hypopnea index also predicted Hct and CMS scores in men after accounting for age, BMI, and SpO 2 during sleep. Finally, heart rate response to hypoxia was lower in men with higher Hct (p < 0.0001). These data support the idea that hypoventilation and decreased ventilatory sensitivity to hypoxia are associated with decreased day time and nighttime SpO 2 levels that may exacerbate the stimulus for erythropoiesis in Andean men and women. However, interventional and longitudinal studies are required to establish the causal relationships between these associations.

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Section: Sleepmentioning

confidence: 87%

Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women

et al. 2020

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“…Evidence at different levels suggests a genetic basis for EE and CMS. Recently, a single-nucleotide polymorphism in the SENP1 gene, which encodes a protease that regulates erythropoiesis, was found to be linked to EE (Zhou et al, 2013 ; Cole et al, 2014 ; Hsieh et al, 2016 ). Furthermore, this association is supported by functional studies at the cellular level where fibroblasts obtained from CMS patients express less SENP1 protein than their healthy counterparts when exposed to hypoxia (Zhou et al, 2013 ).…”

Section: What Causes Cms?mentioning

confidence: 99%

Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

Villafuerte

Corante

2016

High Altitude Medicine & Biology

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Villafuerte, Francisco C., and Noemí Corante. Chronic mountain sickness: clinical aspects, etiology, management, and treatment. High Alt Med Biol. 17:61–69, 2016.—Millions of people worldwide live at a high altitude, and a significant number are at risk of developing Chronic Mountain Sickness (CMS), a progressive incapacitating syndrome caused by lifelong exposure to hypoxia. CMS is characterized by severe symptomatic excessive erythrocytosis (EE; Hb ≥19 g/dL for women and Hb ≥21 g/dL for men) and accentuated hypoxemia, which are frequently associated with pulmonary hypertension. In advanced cases, the condition may evolve to cor pulmonale and congestive heart failure. Current knowledge indicates a genetic predisposition to develop CMS. However, there are important risk factors and comorbidities that may trigger and aggravate the condition. Thus, appropriate medical information on CMS is necessary to provide adequate diagnosis and healthcare to high-altitude inhabitants. After reviewing basic clinical aspects of CMS, including its definition, diagnosis, and common clinical findings, we discuss aspects of its etiology, and address its epidemiology, risk factors, and treatment.

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“…Headache is an important component in the diagnosis of highaltitude deterioration (HAD) and CMS. Traditionally, it was assessed by the headache score scale depending on subjective feelings [1,2,4] . Objective indicators for diagnosis of headache in HA immigrants are missing.…”

Section: Introductionmentioning

confidence: 99%

Pituitary Deformation in High Altitude Immigrants and the Correlation with Headache：A Preliminary Study.

Feng

Xiao

Men

et al. 2021

Preprint

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Aim: To investigate pituitary gland deformation (PGD) in high altitude (HA) immigrants and determine if a correlation exists between PGD with headache and the ratio of brain volume to total intracranial volume (BV/TIV), and to investigate whether PGD can be used as an objective indicator of headache in HA immigrants.Methods: A total of 34 male HA immigrants and 60 age- and gender-matched sea-level (SL) residents were enrolled in this study. 3D T1 weighted brain MRI scans and headache scales were acquired. HA participants were classified into headache positive (HA[+]) and headache negative (HA[-]) subgroups. PGD was graded visually on mid-sagittal images of the pituitary gland. All continuous variables and categorical variables were compared using Student's t-test or Mann-Whitney test and the χ2 or Fisher exact tests, respectively. Kendall's tau rank correlation coefficient and Spearman’s rho were used to investigate the relationship between PGD and headache or BV/TIV, respectively. Receiver operating characteristic (ROC) analysis was used to evaluate whether PGD can be used as an objective indicator of headache in HA immigrants.Results: A higher proportion of HA participants had PGD (54.8%) than SL residents (23.3%) (p=0.005). The proportion of HA(-) participants with PGD (68.2%) was higher than that of HA(+) participants (22.2%) (p=0.044). PGD was negatively correlated with headache (Kendall's tau=-0.323, p=0.0097) and positively correlated with BV/TIV (r=0.454, p=0.010). The presence of PGD was an indicator of headache in HA immigrants (area under the ROC curve=0.712, p= 0.038, sensitivity=0.778, specificity=0.682). Conclusion: A greater proportion of HA immigrants had PGD, which is an adaptation to chronically altered ICP or compliance. The presence of PGD indicated a restoration of spatial compensatory capacity and compliance of intracranial system, leading to headache relief. PGD is a potential indicator of headache in HA immigrants.

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SENP1, but not fetal hemoglobin, differentiates Andean highlanders with chronic mountain sickness from healthy individuals among Andean highlanders

Cited by 17 publications

References 43 publications

Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women

Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women

Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

Pituitary Deformation in High Altitude Immigrants and the Correlation with Headache：A Preliminary Study.

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