Association Between the Polymorphism of Steroid Hormone Metabolism Genes and High-Altitude Pulmonary Edema in the Chinese Han Population.

Purpose: Steroid hormone metabolism plays an essential role in high-altitude pulmonary edema (HAPE) progression. This study aimed to investigate the association between polymorphism in seven steroid hormone metabolism genes (, and ) and HAPE susceptibility among Han Chinese.

Patients And Methods: A total of 41 tagSNPs in the seven genes were genotyped using Sequenom MassARRAY SNP assays from 169 HAPE patients (HAPE-p) and 309 matched Han Chinese individuals resistant to HAPE (HAPE-r).

Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression.

A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance.

The susceptibility gene screening in a Chinese high-altitude pulmonary edema family by whole-exome sequencing.

High-altitude pulmonary edema (HAPE) is one of idiopathic mountain sicknesses that occur in healthy lowlanders when they quickly ascend to altitudes exceeding 2500 m above sea levels within 1-7 days. Growing evidence suggests that genetics plays an important role in the risk of HAPE. In this study, we recruited a Chinese HAPE family and screened genetic variations in the 7 family members (including 6 family members with a medical history of HAPE and the propositus's mother) by whole-exome sequencing.

[Association study between the angiotensin converting enzyme gene insertion/deletion polymorphism and Qinghai Han Chinese with congenital heart disease].

Objective: The aim of this work is to determine whether the angiotensin converting enzyme (ACE) I/D (insertion/deletion) polymorphism is associated with the susceptibility to congenital heart disease (CHD) in the Qinghai Han Chinese.

Methods: This study enrolled 59 CHD patients and 193 CHD controls from Qinghai Cardiovascular Diseases Vocational Hospital. Blood samples were collected from each of the patient and control groups.

Effects of the aqueous extract of a Tibetan herb, Rhodiola algida var. tangutica on proliferation and HIF-1α, HIF-2α expression in MCF-7 cells under hypoxic condition in vitro.

Ethnopharmacological Relevance: Rhodiola algida var. tangutica is a traditional Tibetan herb. Its root and rhizome have been successfully used as an effective clinical remedy for the prevention and treatment of cancer and high-altitude sickness.

CYP17A1 and CYP2E1 variants associated with high altitude polycythemia in Tibetans at the Qinghai-Tibetan Plateau.

Tibetans adapt to high altitude environments through low blood hemoglobin concentrations. Previous work has identified that CYP17A1 and CYP2E1 genes exhibit evidence of local positive selection for this Tibetan high-altitude adaptation. Nevertheless, despite this apparent genetic advantage, some Tibetans still develop high altitude polycythemia (HAPC) yet the reasons for this remain unknown.

EPAS1 Gene Polymorphisms Are Associated With High Altitude Polycythemia in Tibetans at the Qinghai-Tibetan Plateau.

Objective: To test the hypothesis that the polymorphisms in the EPAS1 gene are associated with the susceptibility to high altitude polycythemia (HAPC) in Tibetans at the Qinghai-Tibetan Plateau.

Methods: We enrolled 63 Tibetan HAPC patients and 131 matched healthy Tibetans as a control group, from the Yushu area in Qinghai where the altitude is greater than 3500 m. Eight single-nucleotide polymorphisms (SNPs) of the EPAS1 gene, including rs12619696, rs13420857, rs2881504, rs4953388, rs13419896, rs4953354, rs10187368, and rs7587138, were genotyped by the Sequenom MassARRAY SNP assay.

Sleep disturbances in long-term immigrants with chronic mountain sickness: a comparison with healthy immigrants at high altitude.

The aim of this study was to examine sleep disturbances in patients with chronic mountain sickness (CMS). The sleep of 14 patients with CMS and 11 healthy controls with or without sleep disorders (control N: without sleep disorders; control D: with sleep disorders) was studied by polysomnography. Hypopnea was the sleep disorder most commonly suffered by CMS patients and control D subjects.

No relation between ACE-I/D polymorphism and high altitude pulmonary edema in the Han Chinese.

Objectives: To explore whether the angiotensin I -converting enzyme (ACE) I/D (insertion/ deletion) polymorphism is associated with the susceptibility to high altitude pulmonary edema (HAPE) in the Han Chinese.

Methods: One hundred and forty-seven HAPE-p (HAPE patients) and 193 HAPE-r (HAPE resistants) were enrolled from the Yushu earthquake reconstruction workers in Qinghai province where the altitude is over 3 500 m above sea level. Blood samples were collected from each of the HAPE-p and HAPE-r groups.

[Genome-wide association study of high-altitude pulmonary edema in Han Chinese].

High-altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that is always found among unacclimatized persons after rapid ascent to high altitude, and HAPE is caused by the interaction of genetic and environmental factors. To screen and analyze the susceptibility genes and single nucleotide polymorphisms (SNPs) of HAPE in Han Chinese, the DNA samples of 40 patients with HAPE and 33 healthy controls, who performed the reconstruction tasks from the plain region in Yushu area of Qinghai province during May of 2010 to July of 2012, were scanned by Affymetrix SNP Array 6.0 Chips in this study.

[Serum levels and significance of HIF-1α and HIF-2α in healthy Tibetan and Han residents at different altitudes].

Objective: To explore the serum levels and significance of hypoxic inducible factor (HIF)-1α and HIF-2α in Tibetan and Han residents living at different altitudes.

Methods: A total of 100 healthy adults of Han in plain (altitude 5 m, group P) and Tibetan and Han at moderate altitude (2260 m, groups M1 & M2) and high altitude (4380 m, groups H1 & H2) (n = 20 each) were selected from June 2010 to August 2010. Venous blood samples were collected in the morning.

[Effect of different altitudes on telomere length of rat peripheral blood leukocyte].

The present study was aimed to investigate the effect of different altitudes on telomere length of rat peripheral blood leukocyte and possible mechanism. Sixty male rats were randomly divided into three groups, lower altitude control group (10 m), moderate altitude group (2 260 m) and very high altitude group (simulated 5 000 m). The moderate altitude group and very high altitude group rats were transported to Xining and hypobaric chamber in Qinghai University, respectively.

Excision repair cross-complementation group 1 codon 118 polymorphism, micro ribonucleic acid and protein expression, clinical outcome of the advanced gastric cancer response to first-line FOLFOX-4 in Qinghai-Tibetan plateau population.

Context: The excision repair cross-complementation group 1 (ERCC1) codon 118 C/T polymorphism has been associated with clinical outcome in cancer patients treated with platinum chemotherapy. Ethnic differences in the frequency of this polymorphism have been observed in Caucasian and African populations.

Aim: The aim of this study was to evaluate the frequency and survival benefit of the ERCC1 codon 118 C/T polymorphism in a high-altitude population with advanced gastric cancer.

Neurological adaptations to hypoxia in Tibetan antelope (Pantholops hodgsonii) with a view of molecular biology of respiratory globin-neuroglobin.

Neuroglobin (Ngb) is a respiratory protein that is preferentially expressed in brain of mouse and man. In this article, Tibetan antelope, living at altitude of 3 000-5 000 m for millions of years, was selected as the model of hypoxia-tolerant adaptation species. Using reverse transcription polymerase chain reaction (RT-PCR) and Western blot techniques, expression of Ngb gene was amplified and analyzed in antelope brain tissue.

[Study on the content of myoglobin and the activity of lactate dehydrogenase and malate dehydrogenase in skeletal muscle of tibetan antelope].

Objective: To explore the adaptive mechanism to hypoxia in skeletal muscle of tibetan antelope.

Methods: Tibetan sheep which living at the same altitude (4 300 m) with tibetan antelope and low altitude (1 800 m) sheep as control, the content of myoglobin (Mb) and lactic acid (LA), the activity of lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) in skeletal muscles among three animals were analyzed by spectrophotometer.

Results: The content of myoglobin in skeletal muscle of tibetan antelope significantly higher than that of tibetan sheep and low altitude sheep (P < 0.

Cardiac adaptive mechanisms of Tibetan antelope (Pantholops hodgsonii) at high altitudes.

Objective: To identify cardiac mechanisms that contribute to adaptation to high altitudes in Tibetan antelope (Pantholops hodgsonii).

Animals: 9 male Tibetan antelope and 10 male Tibetan sheep (Ovis aries).

Procedures: Tibetan antelope and Tibetan sheep inhabiting a region with an altitude of 4,300 m were captured, and several cardiac variables were measured.

[Effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19].

This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC.

[Genetic cloning and expression of hypoxia inducible factor 1 alpha in high altitude hypoxic adaptation species Tibetan antelope (Pantholops hodgsonii)].

In order to investigate the role of the hypoxia inducible factor 1 alpha (HIF-1α) in the adaptation mechanism to high altitude hypoxia, the cloning of the HIF-1α gene cDNA of Tibetan antelope (Pantholops hodgsonii), using RT-PCR and RACE, was applied, and the comparative analysis of the tissue-specific expressions of HIF-1α among Tibetan antelope, Tibetan sheep and plain sheep was performed using real-time PCR and Western blot. The sequence analysis indicated that the cDNA sequences acquired by cloning from the HIF-1α gene of Tibetan antelope comprised a 2 471-bp open reading frame (ORF) and a 1 911-bp 3'UTR. The similarity between its coding sequence, predicted amino acid sequence and HIF-1α of other mammals exceeded 87%, in which the similarity with cow was up to more than 98%, which showed that this sequence was the cDNA of HIF-1α of Tibetan antelope.

[Comparisons of endocrine hormones levels between Tibetan antelope and Tibetan sheep].

The Tibetan antelope, a prototype mammal, has developed a unique adaptation to extreme high altitude-associated hypoxia. To investigate the role of the endocrine system in adaptation to high altitude in the Tibetan antelope, comparisons of endocrine hormones levels between Tibetan antelope (n = 9) and Tibetan sheep (n = 10) were performed. Both two kinds of animals were captured at an altitude of 4 300 m and then transported to experimental base at 2 800 m altitude.

[Cloning and homologous analysis of coding region of alpha-globin gene from Tibetan antelope].

Aim: To clone and analyze the encoding region of alpha-globin gene from Tibetan antelope.

Methods: Total RNA was isolated from an adolescent Tibetan antelope liver, and Tibetan antelope alpha-globin gene was amplified by RT-PCR. The PCR product was cloned into pGEM-T vector and sequenced.

A mitochondrial genome sequence of the Tibetan antelope (Pantholops hodgsonii).

To investigate genetic mechanisms of high altitude adaptations of native mammals on the Tibetan Plateau, we compared mitochondrial sequences of the endangered Pantholops hodgsonii with its lowland distant relatives Ovis aries and Capra hircus, as well as other mammals. The complete mitochondrial genome of P. hodgsonii (16,498 bp) revealed a similar gene order as of other mammals.