Cytokine gene polymorphisms in preterm infants with necrotising enterocolitis: genetic association study

¹ Griffith University, Brisbane, Australia
² Royal Maternity Hospital, Belfast, United Kingdom
³ Department of Paediatrics, University of Manitoba, Canada
⁴ The Sequencing Service, College of Life Sciences, University of Dundee, United Kingdom
⁵ NPEU, University of Oxford, United Kingdom
⁶ ANU Medical School, Australia

^* To whom correspondence should be addressed. E-mail: william.mcguire{at}act.gov.au.

Accepted 13 August 2007

	Abstract

Background: The inflammatory cytokine cascade is implicated in the pathogenesis of necrotising enterocolitis (NEC). Genetic association studies of cytokine polymorphisms may help to detect molecular mechanisms that are causally related to the disease process.

Aim: To examine associations between the common genetic variants in candidate inflammatory cytokine genes and NEC in preterm infants.

Methods: Multi-centre case-control and genetic association study. We collected DNA samples from 50 preterm infants with NEC and 50 gestational age and ethnic group frequency-matched controls recruited to a multi-centre case-control study. We genotyped 10 candidate single nucleotide polymorphisms (SNPs) in cytokines previously associated with infectious or inflammatory diseases in preterm infants. The findings were included in random effects meta-analyses with data from previous genetic association studies.

Results: All allele distributions were in Hardy-Weinberg equilibrium. None of the studied cytokine polymorphisms was significantly associated with NEC. We found four previous genetic association studies of cytokine polymorphisms and NEC in preterm infants. Meta-analyses were possible for several SNPs. These increased the precision of the estimates of effect size but did not reveal any significant associations.

Conclusions: The available data are not consistent with more than modest associations between these candidate cytokine variant alleles and NEC in preterm infants. Data from future association studies of these polymorphisms may be added to the meta-analyses to obtain more precise estimates of effects sizes.

Keywords: cytokine, necrotising enterocolitis, polymorphism