PEDIATRICS Vol. 117 No. 6 June 2006, pp. 2285-2286 (doi:10.1542/peds.2006-0104)
COMMENTARY |
A Spitting Image of the Lungs
Department of Pediatrics, University of Lübeck, Lübeck, Germany
Abbreviations: BPD, bronchopulmonary dysplasia • ACE2, angiotensin-converting enzyme 2
In a classical twin-study design, monozygotic twins (who share 100% of their genome) are compared with same-gender dizygotic twins (who share 50% of their genome). In this issue of Pediatrics, Bhandari et al1 report data from a twin study on the incidence of serious diseases of preterm infants. They were able to demonstrate that the risk of developing bronchopulmonary dysplasia (BPD) is significantly increased in monozygotic twins whose siblings are affected. No significant differences between dizygotic and monozygotic twins were observed with regard to intraventricular hemorrhage and necrotizing enterocolitis. According to their data, genetic factors accounted for 
50% of the variance in liability for BPD.
Another, more concealed issue addressed by Bhandari et al in their article relates to the fact that they observe the genetic predisposition to chronic lung disease in a population of infants who are susceptible for BPD because of environmental risk factors.
The importance of environmental risk factors for the development of lung diseases in genetically susceptible individuals is illustrated by recent animal data. Using a knock-out mouse model of the angiotensin-converting enzyme 2 (ACE2) gene, Imai et al2 observed no differences between wild-type and ACE2–knock-out mice when the animals were ventilated after saline instillation into the lungs. However, if the animals were ventilated after experimental induction of sepsis or after acid instillation into the lungs, ACE2-deficient mice (in contrast to wild-type animals) were prone to develop severe acute lung failure.
It is very unlikely that any of the infants studied by Bhandari et al would have developed BPD if they had been delivered at term. They developed BPD because of their genetic susceptibility, their immaturity, and their exposure to measurable environmental factors, which are summarized by Bhandari et al as "treating institution."
These findings have several implications. At this time, no specific genetic polymorphisms that are consistently associated with BPD have been described.3–8 Ongoing genetic-association studies involving thousands of preterm infants will hopefully uncover specific polymorphisms as risk factors for BPD in the near future. The multicenter design of these studies will give us the opportunity to delineate which treatment modalities are associated with worse outcomes in susceptible infants. Furthermore, genes associated with an increased risk of BPD, once identified, will be interesting targets for specific drug therapies.
In their article, Bhandari et al make an attempt to quantify the contribution of genetic factors to the development of BPD for the first time. Their research is an important step toward future studies that explore the genetic and environmental basis of BPD.
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FOOTNOTES |
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Accepted Jan 23, 2006.
Address correspondence to Wolfgang Göpel, MD, Department of Pediatrics, University of Lübeck, 23538 Lübeck, Germany. E-mail: goepel{at}paedia.ukl.mu-luebeck.de
The author has indicated he has no financial relationships relevant to this article to disclose.
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REFERENCES |
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- Bhandari V, Bizzarro MJ, Shetty A, et al. Familial and genetic susceptibility to major neonatal morbidities in preterm twins.
Pediatrics. 2006;117
:1901
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[Abstract/Free Full Text] - Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436 :112 –116[CrossRef][Medline]
- Yanmandra K, Loggins J, Baier RJ. The angiotensin converting enzyme insertion/delition polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants. BMC Pediatr. 2004;4 :26[Medline]
- Kazzi SN, Quasney MW. Deletion allele of angiotensin-converting enzyme is associated with increased risk and severity of bronchopulmonary dysplasia. J Pediatr. 2005;147 :818 –822[Medline]
- Yanamandra K, Boggs P, Loggins J, Baier RJ. Interleukin 10 -1082 G/A polymorphism and risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants. Pediatr Pulmonol. 2005;39 :426 –432[Medline]
- Lin HC, Su BH, Chang JS, Hsu CM, Tsai CH, Tsai FJ. Nonassociation of interleukin 4 intron 3 and 590 promoter polymorphisms with bronchopulmonary dysplasia for ventilated preterm infants. Biol Neonate. 2005;87 :181 –186[Medline]
- Kazzi SN, Kim UO, Quasney MW, Buhimschi I. Polymorphism of tumor necrosis factor-alpha and risk and severity of bronchopulmonary dysplasia among very low birth weight infants. Pediatrics. 2004;114 (2). Available at: www.pediatrics.org/cgi/content/full/114/2/e243
- Weber B, Borkhardt A, Stoll-Becker S, Reiss I, Gortner L. Polymorphisms of surfactant protein A genes and the risk of bronchopulmonary dysplasia in preterm infants. Turk J Pediatr. 2000;42 :181 –185[Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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