Heterozygotes of NOS3 Polymorphisms Contribute to Reduced Nitrogen Oxides in High-Altitude Pulmonary Edema

Ahsan, Aarif; Mohd, Ghulam; Norboo, Tsering; Baig, Masroor A.; Pasha, M. A. Qadar

doi:10.1378/chest.130.5.1511

Cited by 55 publications

(47 citation statements)

References 34 publications

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“…Single-locus analysis suggested a positive association of the G allele of rs8066114 and the T allele of rs4461142 with HAPE under the dominant model of inheritance. 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).…”

Section: Discussionmentioning

confidence: 78%

“…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: 78%

“…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: 78%

Section: Discussionmentioning

confidence: 78%

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

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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show abstract

“…Accumulating evidence suggests that the excessive pulmonary response in HAPE-prone individuals is due to reduced nitric oxide (NO) bioavailability under hypoxic conditions (Dehnert et al, 2007). Consistent with this premise, single nucleotide polymorphisms (SNPs) in NO synthase 3, which is involved in NO synthesis, have been associated with HAPE susceptibility (Droma et al, 2002;Ahsan et al, 2006). In addition, the renin-angiotensin-aldosterone cascade may also play an important role in the pathogenesis of HAPE; SNPs in angiotensin-converting enzyme (Hotta et al, 2004) and have been positively correlated with risk for HAPE.…”

Section: Introductionmentioning

confidence: 97%

Mitochondrial haplogroup D4 confers resistance and haplogroup B is a genetic risk factor for high-altitude pulmonary edema among Han Chinese

Luo¹,

Gao²,

Li³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. High-altitude pulmonary edema (HAPE) is a lifethreatening condition caused by acute exposure to high altitude. Accumulating evidence suggests that genetic factors play an important role in the etiology of HAPE. However, conclusions from association studies have been hindered by limited sample size due to the rareness of this disease. It is known that mitochondria are critical for hypoxic adaptation, and mitochondrial malfunction can be an important factor in HAPE development. Therefore, we tested the hypothesis that ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (4): 3658-3667 (2012) Mitochondrial haplogroup and HAPE susceptibility 3659 mitochondrial DNA haplotypes and polymorphisms affect HAPE susceptibility. We recruited 204 HAPE patients and 174 healthy controls in Tibet (3658 m above sea level), all Han Chinese, constituting the largest sample size of all HAPE vulnerability studies. Among mtDNA haplogroups, we found that haplogroup D4 is associated with resistance to HAPE, while haplogroup B is a genetic risk factor for this condition. Haplogroup D4 (tagged by 3010A) may enhance the stability of 16S rRNA, resulting in reduced oxidative stress and protection against HAPE. Within haplogroup B, subhaplogroup B4c (tagged by 15436A and 1119C) was associated with increased risk for HAPE, while subhaplogroup B4b may protect against HAPE. We indicate that there are differences in HAPE susceptibility among mtDNA haplogroups. We conclude that mitochondria are involved in adverse reactions to acute hypoxic exposure; our finding of differences in susceptibility as a function of mitochondrial DNA haplotype may shed light on the pathogenesis of other disorders associated with hypoxia, such as chronic obstructive pulmonary disease.

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Human adaptability studies at high altitude: Research designs and major concepts during fifty years of discovery

Beall

2013

American J Hum Biol

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Details of the proximate mechanisms, the biochemical, and physiological processes underlying the three modes of biological adaptation are accumulating. Better understanding of oxygen-homeostasis processes leads to questions about crossadaptation with other environmental factors. The particulars of the ultimate mechanisms, the evolutionary, and microevolutionary history underlying the population differences are also emerging. For example, similar hemoglobin phenotypes among Tibetan and Ethiopian Amhara highlanders associate with different genetic loci and the variants at those loci are present in most populations regardless of altitude. Continuing fieldwork is urgent because modernization and migration are changing the traditional ways of life and patterns of exposure to the environment among highlanders everywhere.

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Heterozygotes of NOS3 Polymorphisms Contribute to Reduced Nitrogen Oxides in High-Altitude Pulmonary Edema

Cited by 55 publications

References 34 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

Mitochondrial haplogroup D4 confers resistance and haplogroup B is a genetic risk factor for high-altitude pulmonary edema among Han Chinese

Human adaptability studies at high altitude: Research designs and major concepts during fifty years of discovery

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