Endothelial Nitric Oxide Synthase Gene Polymorphisms Associated with Susceptibility to High Altitude Pulmonary Edema in Chinese Railway Construction Workers at Qinghai-Tibet over 4 500 Meters above Sea Level

Sun, Yujing; Fang, Ming-wu; Niu, Wenquan; Li, Guangping; Liu, Jing-liang; Ding, Shou-quan; Xu, Ying; Yu, Guo-shu; Dong, Jiyan; Pan, Yunjun; Dong, Wei-Ya; Cao, Jing-wen; Li, Xiaobo; Wang, Zhongxiang; Yu, Guang-xue; Sun, Hui-cheng; Jia, Zhong-hou; Wang, Xiaoming; Qin, Si; Wu, Qiulian; Zhou, Wu-qing; Zhu, Tongchun; Qiu, Changchun

doi:10.1016/s1001-9294(11)60005-9

Cited by 13 publications

(10 citation statements)

References 29 publications

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“…Although no significant associations were found for any of the other four polymorphisms, their corre- (Ahsan et al 2006;Su et al 2007), which may lead to HAPE. Although the association between NOS3 gene variants and HAPE susceptibility has been previously assessed in a number of studies, the results have not been consistent, especially for the NOS3 rs1799983 (G894T) polymorphism (Droma et al 2002;Weiss et al 2003;Ahsan et al 2004Ahsan et al , 2006Sun et al 2010). In our case-control cohort of Han Chinese, there was a significant association between the rs1799983 (G894T) polymorphism and HAPE susceptibility; this finding suggests that this particular SNP may be an Asian-specific risk factor of HAPE.…”

Section: Discussionmentioning

confidence: 97%

“…Eligible studies: Five studies (Droma et al 2002;Weiss et al 2003;Ahsan et al 2004Ahsan et al , 2006Sun et al 2010) met the inclusion/exclusion criteria and were selected for meta-analysis. When the subjects from these studies were combined with our case-control cohort, a total of 399 HAPE cases and 495 non-HAPE controls were available for analysis.…”

Section: Meta-analysis Of Nos3 Gene Rs1799983 (G894t) Polymorphism Anmentioning

confidence: 99%

“…Specifically, an Alu insertion/deletion (I/D) poly morphism consisting of presence or absence of a 278-bp long fragment (rs4340), the single nucleotide polymorphisms (SNPs) A240T (rs4291) and A2350G (rs4343), three tag SNPs of the ACE gene, and the NOS3 gene G894T (rs1799983) SNP were systematically investigated. Several previous case-controlled studies have analyzed the association of the NOS3 G894T SNP with HAPE (Droma et al 2002;Weiss et al 2003;Ahsan et al 2004Ahsan et al , 2006Sun et al 2010), but the findings have been contradictory, possibly due to inadequate sample sizes and limitations in the casecontrol selection. Therefore, we expanded our analysis of this polymorphism to include a meta-analysis of published data from both the English and Chinese literature and our own unpublished data to further assess the association of NOS3 G894T SNP with HAPE.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of Angiotensin Converting Enzyme and Nitric Oxide Synthase 3 Genes as Risk Factors of High-Altitude Pulmonary Edema: A Case-Control Study and Meta-Analysis

Wang

Huang

et al. 2013

Tohoku J. Exp. Med.

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High-altitude pulmonary edema (HAPE) is a non-cardiogenic type of pulmonary edema developing altitudes >2,500 m. Angiotensin converting enzyme (ACE) and nitric oxide synthase 3 (NOS3) play important roles in regulating pulmonary vascular tone. To assess associations between genetic variants in the ACE and NOS3 genes and HAPE risk, 27 HAPE patients and 108 matched controls were genotyped and analyzed. The indicated HAPE association of the NOS3 G894T (Glu298Asp) single nucleotide polymorphism (SNP), which may change NO production, was further evaluated by a meta-analysis of six studies involving 399 HAPE patients and 495 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined with fixed-effects models. Stratification analyses of ethnicity and geographic location were performed. Significant associations were observed for the dominant model in two ACE tag SNPs influencing serum ACE concentrations (rs8066114 polymorphism: GG+CG vs. CC; rs4461142 polymorphism: TT+CT vs. CC). Furthermore, Single-locus analysis indicated significantly different distributions of G allele frequency between the cases (29.63%) and controls (17.13%) for the ACE rs8066114 polymorphism. The casecontrol distributions of genotype frequencies and T allele frequency of NOS3 G894T (Glu298Asp) polymorphism were significantly higher in the cases than controls, and the NOS3 G894T (Glu298Asp) SNP showed elevated HAPE risk under the dominant model (TT+GT vs. GG). Meta-analysis showed overall association of NOS3 G894T SNP with HAPE risk under the allele contrast and dominant genetic models, which remained significant for Asians. In conclusion, ACE rs8066114 and rs4461142 and NOS3 rs1799983 (G894T) polymorphisms may be associated with increased HAPE risk in Asians.

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Section: Discussionmentioning

confidence: 97%

Section: Meta-analysis Of Nos3 Gene Rs1799983 (G894t) Polymorphism Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of Angiotensin Converting Enzyme and Nitric Oxide Synthase 3 Genes as Risk Factors of High-Altitude Pulmonary Edema: A Case-Control Study and Meta-Analysis

Wang

Huang

et al. 2013

Tohoku J. Exp. Med.

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“…They concluded that these singlenucleotide polymorphisms in the eNOS gene could be genetic markers for predicting the susceptibility to HAPE 61) . eNOS gene polymorphisms have also been shown to be associated with susceptibility to HAPE in the Chinese population 62) . However, these studies do not give definite conclusive statements.…”

Section: Nitric Oxide Synthase (Nos): This Gene Exists In Three Formsmentioning

confidence: 99%

High‐altitude Pulmonary Edema: Review

Bhagi

Srivastava

Singh

2014

Journal of Occupational Health

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High‐altitude Pulmonary Edema: Review: Shuchi BHAGI, et al. Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), India— Objective At High altitude (HA) (elevation >2,500 m), hypobaric hypoxia may lead to the development of symptoms associated with low oxygen pressure in many sojourners. High‐altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non‐acclimatized healthy individuals. It is a multifactorial disease involving both environmental and genetic risk factors. Since thousands of lowlanders travel to high altitude areas for various reasons every year, we thought it would be interesting to review pathological aspects related to hypobaric hypoxia, particularly HAPE. Method Since the pathogenesis of HAPE is still a subject of study, we systematically identified and categorized a broad range of facets of HAPE such as its incidence, symptoms, physiological effects, pathophysiology including physiological and genetic factors, prevention and treatment. Results This review focuses on HA‐related health problems in general with special reference to HAPE, which is one of the primary causes of deaths at extreme altitudes. Hence, it is extremely important, as it summarizes the literature in this area and provides an overview of this severe HA malady for evaluation of physiological, biochemical and genetic responses during early induction and acclimatization to HA. This article could be of broad scientific interest for researchers working in the field of high altitude medicine.

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“…Highland indigenous populations like Tibetans have high NO levels in the lung, plasma, and red blood cells that were at least double the levels that can be found in other populations regardless of altitude. With respect to NOS3 G894T and its relation to athletic performance or status, the over-representation of the GG genotype and G allele in all athletes suggests that the G894 allele may favor many types of sports [27,28]. This supports the adaptive function of 894G allele and genotype.…”

Section: Endothelial Nitric Oxide Synthase (Enos): (Rs1799983 G894tmentioning

confidence: 85%

Placental Adaptation to Hypoxia as a Predictive Marker for Preeclampsia

Ahmed¹

2019

Prediction of Maternal and Fetal Syndrome of Preeclampsia

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The ability of the placenta to interact with surrounding microenvironment of hypoxia can serve as a predictive marker for the development of preeclampsia. Lessons can be studied from highlands inhabitants and their ability to survive extreme conditions of hypobaric hypoxia. Many candidate genes loci that are associated with adaptation to high altitude hypoxia and healthy exercise are also associated with adaptation to hypoxia in normal pregnancy. This can pave the way to a new approach based on the concept of evolution and adaptation stating that "genes can undergo a process of natural selection for the fittest adaptive variants, so as to reach a state of adaptation to the scarce microenvironments." Accordingly, the degree of adaptation in candidate genes and their polymorphisms can serve as predictive markers for the development of preeclampsia. This can be seen in the high degree of concordance between gene expression and the lesions seen in the placenta and other remote organs in the different subtypes of preeclampsia. To conclude, "adaptive or less adaptive" can be the genetic result that answers the question of disease prediction, recurrence, and possible complications.

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Endothelial Nitric Oxide Synthase Gene Polymorphisms Associated with Susceptibility to High Altitude Pulmonary Edema in Chinese Railway Construction Workers at Qinghai-Tibet over 4 500 Meters above Sea Level

Cited by 13 publications

References 29 publications

Polymorphisms of Angiotensin Converting Enzyme and Nitric Oxide Synthase 3 Genes as Risk Factors of High-Altitude Pulmonary Edema: A Case-Control Study and Meta-Analysis

Polymorphisms of Angiotensin Converting Enzyme and Nitric Oxide Synthase 3 Genes as Risk Factors of High-Altitude Pulmonary Edema: A Case-Control Study and Meta-Analysis

High‐altitude Pulmonary Edema: Review

Placental Adaptation to Hypoxia as a Predictive Marker for Preeclampsia

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