Polymorphisms of Renin-Angiotensin System Genes With High-Altitude Pulmonary Edema in Japanese Subjects

Hotta, Junichi; Hanaoka, Masayuki; Droma, Yunden; Katsuyama, Yoshihiko; Ôta, Masao; Kobayashi, Toshio

doi:10.1378/chest.126.3.825

Cited by 67 publications

(61 citation statements)

References 29 publications

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“…Several previous studies have assessed the association between HAPE susceptibility and the ACE I/D (rs4340) polymorphism, but the results have been inconsistent (Kumar et al 2004;Hotta et al 2004;Stobdan et al 2011).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…5,19,20 Considering the wide CIs generated by these associations, it is possible that the study power was insufficient to detect or replicate a real result. It is an inevitable problem for HAPE genetic identification because the incidence is relatively low, with estimates ranging from 0.1-4.0%.…”

Section: Discussionmentioning

confidence: 99%

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis

Sun

Zhu

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Background and objective: High-altitude pulmonary oedema (HAPE) is a non-cardiogenic hydrostatic oedema involving a genetic component. Considering the low incidence of HAPE, sample sizes in current reports are relatively limited. We aimed to assess the association between the angiotensin-converting enzyme (ACE) I/D polymorphism and HAPE via a meta-analysis of published and unpublished data. Materials and methods:We searched PubMed, CBM, CNKI, and Cochrane Library Database before 20 November 2010. A random-effects model was applied (STATA) and study quality was assessed in duplicate.Results: A total of five studies including 305 cases and 662 controls were meta-analysed. The summary odds ratio (OR) indicated that no significant differences in risk of developing HAPE were found between carriers of ACE D and I alleles (OR = 1.20; 95% confidence interval (CI), 0.98-1.48; p = 0.084). Lack of association persisted for genotypes under the recessive mode. However, genotype association under the dominant mode showed D allele carriers significantly conferred a 1.55-fold increased HAPE risk compared with II genotype carriers (95% CI, 1.15-2.08; p = 0.004). Funnel plot and Egger's test suggested no evidence of publication bias. Conclusions: Our results supported the notion that ACE D allele carriers were at significant increased risk of developing HAPE.

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“…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. Furthermore, synergistic effects of genetic polymorphisms in angiotensin-converting enzyme and aldosterone synthase CYP11B2 confer a high predisposition to HAPE in Han Chinese (Qi et al, 2008).…”

Section: Introductionmentioning

confidence: 89%

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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Polymorphisms of Renin-Angiotensin System Genes With High-Altitude Pulmonary Edema in Japanese Subjects

Cited by 67 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

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis

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

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