Molecular Genetics of Predisposition to Respiratory Disorders in Newborn


During the perinatal period, preterm neonates face severe complications. These include disorders of the lung such as respiratory distress syndrome and chronic lung disease. The risk of complications depends on maturity, but data also suggest the existence of an inherited susceptibility. This may be due to genetic polymorphisms and inherited mutations. Reported associations between lung disease and polymorphisms of genes encoding proteins that regulate inflammation, vasoregulation and lung development helped the identification of specific genetic elements in perinatal respiratory disorders. In a minority of newborns inherited mutations such as those of surfactant protein encoding gene may be responsible for the development of perinatal lung disorders. Further studies are required to assess those genetic patterns that can be used for the identification of patients at risk.

Key concepts:

  • Perinatal respiratory disorders affect primarily preterm infants.

  • These include idiopathic respiratory disorder, bronchopulmonary dysplasia.

  • Inherited genetic polymorphisms may be a risk factor of these complications.

  • Genetic polymorphisms with an impact on immune response, vasoregulation and lung development are extensively tested.

  • Several associations between polymorphisms and disease were reported.

  • Other data support the contribution of genetics to other perinatal complications that are risk factors for respiratory disorders.

  • Rare mutations may also cause perinatal lung disorders in some infants.

  • One day the results of these studies may serve as a basis for individualized therapy and risk assessment; currently we are far from this goal.

Keywords: preterm neonate; genetic polymorphism; complication; idiopathic respiratory disorder; bronchopulmonary dysplasia

Figure 1.

Connections and sequences between respiratory disorders and other perinatal complications.

Figure 2.

Interactions between products of genes tested in genetic polymorphism studies in preterm neonates. This schematic figure presents those related specifically to the newborn lung. For specific elements contributing to inflammation (see Figure ). TGFβ, transforming growth factorβ; VEGF, vascular endothelial growth factor; and IGF, insulin‐like growth factor. The genetic polymorphisms of four surfactant proteins (SP) are also widely investigated.

Figure 3.

Interactions between products of genes tested in genetic polymorphism studies in preterm neonates: their contribution to inflammatory response resulting in organ damage. ACE, angiotensin‐converting enzyme; AT, angiotensin receptor; AI and AII, angiotensin I and II; VEGF, vascular endothelial growth factor; IGF, insulin‐like growth factor; IL, interleukin; TNF, tumour necrosis factor; CARD, caspase recruitment domain; ER, estrogen receptor; HSP, heat shock protein; MBL, mannose binding lectine; TLR, toll‐like receptor; and IFN, interferon.

Figure 4.

Some of the reported associations between genotype and perinatal complications. TNF, tumor necrosis factor; IL, interleukin; ACE, angiotensin converting enzyme; ER, estrogen receptor; SP, surfactant protein; MMP, matrix metalloprotease; VEGF, vascular endothelial growth factor; GST, glutation‐S‐transferase; LT, lymphotoxin; and MBL, mannose‐binding lectin. Single nucleotide genetic polymorphisms are presented as [A]number[B], where [A] and [B] refer to nucleotide in the majority and the minority of people, respectively and the number indicates the position of polymorphism. In other polymorphisms the changed amino acids (such as Val/Leu), the restriction site of the enzyme used for polymorphism detection (PVUII) or the presence of insertion/deletion sequence are indicated. (Bokodi et al., ).



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Further Reading

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Esplin MS (2006) Preterm birth: a review of genetic factors and future directions for genetic study. Obstetrics and Gynecological Survey 61: 800–806.

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Nesin M (2007) Genetic basis of preterm birth. Frontiers in Bioscience 12: 115–124.

Park JS, Park CW, Lockwood CJ and Norwitz ER (2005) Role of cytokines in preterm labor and birth. Minerva Ginecologica 57: 349–366.

Ward RM and Beachy JC (2003) Neonatal complications following preterm birth. British Journal of Obstetrics and Gynaecology 110: 8–16.

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Tulassay, Tivadar, Treszl, Andras, and Vasarhelyi, Barna(Sep 2009) Molecular Genetics of Predisposition to Respiratory Disorders in Newborn. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021449]