The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

Yanamandra, Krishna; Loggins, John; Baier, R J

doi:10.1186/1471-2431-4-26

Cited by 32 publications

(31 citation statements)

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“…[19][20][21][22][23] In humans, polymorphisms in surfactant protein A & B, TNF-α, angiotensin-converting enzyme and gluthathione-S-transferase-P1 genes, genes, and having known altered biological functions, have been linked in small studies with variations in risk of BPD or its severity, [24][25][26][27] although others have failed to show similar associations in independent populations. 28,29 PDA persistence was also largely heritable in our analysis, a finding that is consistent with a significant contribution of individual's ethnic background to susceptibility. 30 PDA closure mainly depends on circulating levels of endogenous prostaglandins, produced by cyclooxygenase (COX), in addition to nitric oxide (NO) which mediates ductal relaxation in highly immature neonates.…”

Section: Discussionsupporting

confidence: 70%

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

2008

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Objective-The goal was to determine the magnitude of genetic effects on susceptibility and risk factors for bronchopulmonary dysplasia by using the clinically validated National Institutes of Health consensus definition as a demonstrated proxy for long-term respiratory and neurodevelopmental outcomes in extremely low birth weight infants.Methods-We analyzed clinical data from twin pairs born at ≤30 completed weeks gestation in British Columbia, Canada, between 1993 and 2006. Differences in correlations between monozygotic (MZ) and dizygotic (DZ) twin pairs and model-fitting approaches were used to quantify the relative contribution of genetic, shared environmental and non-shared environmental effects.Results-Among 318 twins of known zygosity, monozygotic twin pair similarities were greater than those observed for dizygotic pairs, which suggest significant heritability for bronchopulmonary dysplasia. Model-fitting analyses confirmed that genetic effects accounted for 82% and 79% of the observed variance in bronchopulmonary dysplasia susceptibility, defined on the basis of the need for supplemental oxygen at 36 weeks or the National Institutes of Health consensus definition, respectively. Variations in rates of hemodynamically significant PDA were largely accounted for by genetic effects, whereas variance in susceptibility to blood-borne bacterial infections was largely attributable environmental factors both common and unique to each infant.Conclusions-Susceptibility to BPD and persistence of PDA are both significantly heritable. Our study strengthens the case for investigating further genetic risk stratification markers useful for predicting the most significant long-term respiratory and neurodevelopmental consequences of bronchopulmonary dysplasia in premature neonates.

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Section: Discussionsupporting

confidence: 70%

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

2008

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“…11 Various genetic markers such as factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin II gene polymorphisms have been found to be risk factors for IVH. 20,21 Similarly, we have shown the relationship between several ILs and vascular gene markers with many conditions of prematurity in VLBW premature infants receiving ventilation therapy. [20][21][22] In the present investigation, we studied the association of eNOS gene promoter polymorphism T-786C with the origin of respiratory and IVH conditions in premature African American infants.…”

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confidence: 78%

Is an endothelial nitric oxide synthase gene mutation a risk factor in the origin of intraventricular hemorrhage?

Vannemreddy¹,

Notarianni²,

Yanamandra

et al. 2010

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Object Studies have shown decreased levels of nitric oxide (NO), the product of endothelial NO synthase (eNOS) gene activity, in infants with respiratory conditions and intraventricular hemorrhage (IVH). The authors evaluated the association of the eNOS gene promoter polymorphism T-786C with the cause of these conditions (respiratory conditions and IVH) in premature infants. Methods Blood samples from 124 African American premature infants were studied. The DNA was isolated and microplate polymerase chain reaction–restriction fragment length polymorphism assay was performed. Genotypes were scored as: TT homozygotes with 140 bp and 40 bp; CC homozygotes with 90 bp, 50 bp, and 40 bp; and TC heterozygotes with 140 bp, 90 bp, 50 bp, and 40 bp. Genotypes were stratified according to ethnicity, preterm status, and prematurity conditions. Results The mutant allele -786C was present in 15.3% of premature infants with respiratory distress syndrome, bronchopulmonary dysplasia, and IVH, compared with 7.25% in those premature infants without these conditions. A significant 2-fold increase of the mutant allele in patients compared with controls (p = 0.04, OR 2.3) reveals that the eNOS -786C allele could be a significant risk factor in the origin of respiratory conditions and IVH in premature infants. Conclusions These results suggest that the mutant eNOS -786C allele is a significant risk factor in the origin of respiratory and IVH diseases, probably mediating an insufficient supply of endogenous NO in premature infants.

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“…Although this polymorphism appears to affect factor VII coagulant activity in healthy subjects, the significance of this surprising association is obscure [43]. Similarly, an intronic repeat sequence variant within the angiotensin-converting enzyme gene was shown to influence BPD susceptibility [44], but again findings could not be replicated [45]. Other associations with polymorphisms in genes encoding for cytokines critical to the development of adaptive immune responses (i.e.…”

Section: Genetic Associations For Bpd: Current State Of Knowledgementioning

confidence: 82%

Genetics of bronchopulmonary dysplasia in the age of genomics

Lavoie

Dubé

2010

Current Opinion in Pediatrics

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Purpose of review-According to recent evidence, susceptibility to bronchopulmonary dysplasia (BPD) in preterm infants is predominantly inherited. The purpose of this review is to discuss current published genetic association studies in light of the accumulated knowledge in genomics.Recent findings-Major advances in the development of next generation genotyping and sequencing platforms, statistical methodologies, inventories of functional outcome of some common genetic polymorphisms and large scale cataloguing of genetic variability among many of the world's ethnic populations have greatly facilitated the study of polygenic conditions. For BPD, genetic association studies have primarily focused on components of innate (e.g. first-line) immune and anti-oxidant defences, mechanisms of vascular and lung remodelling, and surfactant proteins. However, studies have been limited in sample size and therefore fraught with a high probability of false-positive and false-negative associations. Nonetheless, candidate gene associations have indicated some novel biological pathways and provide a conceptual framework for the design of larger, collaborative population-based studies.Summary-Although studies to date have not been able to identify reproducible genetic risk markers for BPD, they have directed us towards new, promising research avenues.

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The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

Cited by 32 publications

References 32 publications

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

Is an endothelial nitric oxide synthase gene mutation a risk factor in the origin of intraventricular hemorrhage?

Genetics of bronchopulmonary dysplasia in the age of genomics

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