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Association of interferon γ T+874A and interleukin 12 p40 promoter CTCTAA/GC polymorphism with the need for respiratory support and perinatal complications in low birthweight neonates
  1. G Bokodi1,
  2. L Derzbach1,
  3. I Bányász1,
  4. T Tulassay2,
  5. B Vásárhelyi2
  1. 1First Department of Pediatrics, Semmelweis University, Budapest, Hungary
  2. 2Research Group of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary
  1. Correspondence to:
    G Bokodi
    First Department of Pediatrics, Semmelweis University Budapest, Bókay u 53 H-1083, Hungary; bokodi{at}gyer1.sote.hu

Abstract

Background: Data support the role of interferon (IFN)γ and interleukin (IL)12 in perinatal complications. IFNγ T+874A and IL12 p40 promoter CTCTAA/GC polymorphisms may have an effect on cytokine production.

Methods: DNA was extracted from dried blood samples of 153 low birthweight (LBW) infants and 172 healthy term infants. IFNγ and IL12 genetic polymorphisms were determined to investigate the association between polymorphisms and ventilation characteristics, bronchopulmonary dysplasia (BPD) and other perinatal disorders.

Results: The IFNγ+874A allele was over-represented in LBW infants. Carriers of the IFNγ+874T allele required mechanical ventilation and oxygen supplementation for time periods 41% and 35%, respectively, shorter than those required by those not carrying the IFNγ+874T allele. Stepwise logistic regression analysis showed that carriers of the IFNγ+874T allele were protected against BPD (odds ratio (OR) 0.35 (95% confidence interval (CI) (0.12 to 0.99))) and patent ductus arteriosus (OR 0.43 (95% CI 0.19 to 0.97)), whereas carriers of the IFNγ+874A allele were at higher risk of severe hypotension (OR 3.40 (95% CI 1.01 to 11.52)) and respiratory distress syndrome (OR 4.03 (95% CI 1.30 to 12.50)). Carriers of the IL12 GC allele were protected against pneumonia (OR 0.32 (95% CI 0.14 to 0.75)). Carriers of the IL12 CTCTAA allele were at higher risk of developing necrotising enterocolitis (NEC; OR 2.37 (95% CI 1.01 to 5.53)).

Conclusions: Carrier state of the IFNγ+874A allele presents an increased risk for premature birth and lung damage, as well as other perinatal complications. The risks of pneumonia and NEC are higher in heterozygotic carriers of the IL12 CTCTAA/GC polymorphism. Further studies are needed to determine whether these associations are the result of altered cytokine-producing capacity in infants carrying the tested alleles.

  • BPD, bronchopulmonary dysplasia
  • IFN, interferon
  • IVH, intraventricular haemorrhage
  • IRDS, idiopathic respiratory distress syndrome
  • LBW, low birthweight
  • NEC, necrotising enterocolitis
  • PCR, polymerase chain reaction
  • PDA, patent ductus arteriosus
  • RFLP, restriction fragment length polymorphism
  • SNP, single-nucleotide polymorphism
  • TNF, tumour necrosis factor

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Footnotes

  • Published Online First 5 June 2006

  • Funding: This study was financially supported by OTKA Grant T046056 and GVOP-3-1-1/2004-300.

  • Competing interests: None.

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