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PEDIATRICS Vol. 112 No. 4 October 2003, pp. 800-803

Is Interleukin-6 –174 Genotype Associated With the Development of Septicemia in Preterm Infants?

David Harding, PhD^*, Sukhbir Dhamrait, MD, Ann Millar, MD, Steve Humphries, PhD, Neil Marlow, MD^||, Andrew Whitelaw, MD^¶ and Hugh Montgomery, MD

^* Department of Child Health, University of Bristol, Bristol, United Kingdom
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, United Kingdom
Lung Research Group, University of Bristol Medical School, Southmead Hospital, Bristol, United Kingdom
^|| School of Human Development, University of Nottingham, Nottingham, United Kingdom
^¶ Neonatal Intensive Care Unit, University of Bristol Medical School, Southmead Hospital, Bristol, United Kingdom

Objective. Systemic infection affects one quarter of preterm infants. Defense from infection is in part mediated by the cytokine interleukin-6 (IL-6). We tested the hypothesis that the IL-6 –174 GG genotype, associated with lower IL-6 response to inflammation, is also associated with the development of septicemia in preterm infants.

Methods. The study group comprised 157 infants who were born at 32 weeks. Genotype distribution (34% [54] GG, 46% [72] GC, 20% [31] CC) and C allele frequency (0.43; 95% confidence interval [CI]: 0.37–0.48) were similar to the UK adult population. Among the patients who developed bacterially confirmed septicemia (n = 51 [33%]), there was a significantly higher prevalence of the IL-6 –174 GG genotype than that observed in those who did not develop infection (47% vs 28% for GG: odds ratio [OR]: 2.3; 95% CI: 1.1–4.5). This association remained statistically significant (OR: 2.7; 95% CI: 1.2–6.3) after multiple binary logistic regression adjustment for other significant predictors of the development of septicemia. Late infection alone was similarly associated with GG genotype (septicemia 47% vs no septicemia 29% for GG: OR: 2.2; 95% CI: 1.1–4.3).

Conclusions. Variation in the IL-6 gene seems to influence the defense against bacterial pathogens in the very preterm infant.

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Key Words: interleukin-6 • polymorphism • infant • infection

Abbreviations: NICU, neonatal intensive care unit • IL-6, interleukin-6 • APIP, Avon Premature Infant Project • OR, odds ratio • CI, confidence interval

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Received for publication Aug 12, 2002; Accepted Jun 13, 2003.

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