Genetic basis of apnoea of prematurity and caffeine treatment response: role of adenosine receptor polymorphisms: genetic basis of apnoea of prematurity

Acta Paediatr. 2012 Jul;101(7):e299-303. doi: 10.1111/j.1651-2227.2012.02664.x. Epub 2012 Mar 29.

Abstract

Aim: Caffeine treatment reduces the frequency of apnoea of prematurity (AOP) and eliminates the need for mechanical ventilation by acting as a nonspecific inhibitor of adenosine A1 and adenosine 2A receptors. Patients with AOP have demonstrated variant responses to caffeine therapy. We proposed to investigate the role of A1 and 2A polymorphisms in the development of AOP and individual differences in caffeine response. Secondly, we aimed to determine whether these polymorphisms have any effect on bronchopulmonary dysplasia (BPD) development.

Methods: Cord blood samples were collected from infants born with gestational ages between 24 and 34 weeks. Two groups were defined: patients without apnoea (n = 60) and patients with apnoea (n = 55). Patients with apnoea were divided into two subgroups: a caffeine-responsive group (n = 30) and an unresponsive group (n = 25). Six single-nucleotide polymorphisms were chosen for genotyping.

Results: Patients with apnoea over 28 weeks of gestational age who responded to the caffeine treatment were found to carry the rs16851030 C/C genotype rather than the C/T or T/T genotype. Logistic regression analysis showed a significant correlation between rs35320474-C/T and T/T genotypes and apnoea and BPD development.

Conclusion: Our results indicate a role for adenosine receptor gene polymorphisms in susceptibility to AOP and BPD and in interindividual variability to caffeine response.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchopulmonary Dysplasia / genetics
  • Caffeine / therapeutic use*
  • Case-Control Studies
  • Citrates / therapeutic use*
  • Drug Administration Schedule
  • Genetic Markers
  • Genotype
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy
  • Infant, Premature, Diseases / genetics*
  • Logistic Models
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Purinergic P1 Receptor Antagonists / therapeutic use*
  • Receptor, Adenosine A1 / genetics*
  • Receptors, Adenosine A2 / genetics*
  • Sleep Apnea Syndromes / drug therapy
  • Sleep Apnea Syndromes / genetics*
  • Treatment Outcome

Substances

  • Citrates
  • Genetic Markers
  • Purinergic P1 Receptor Antagonists
  • Receptor, Adenosine A1
  • Receptors, Adenosine A2
  • Caffeine
  • caffeine citrate