Tohoku J. Exp. Med., 2019 April, 247(4)

Association between Tumor Necrosis Factor-α Promoter -308 G/A Polymorphism and Early Onset Sepsis in Preterm Infants

TATJANA VARLJEN,¹ OLGICA RAKIC,² GORDANA SEKULOVIC,² BILJANA JEKIC,³ NELA MAKSIMOVIC,³ MILICA RANKOVIC JANEVSKI,² IVANA NOVAKOVIC³ and TATJANA DAMNJANOVIC³

¹Institute of Legal Medicine, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
²Institute of Neonatology, Belgrade, Serbia
³Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Early-onset neonatal sepsis (EOS) is diagnosed during the first 7 days of neonatal life and is the major cause of morbidity and mortality among preterm infants. Genetic predisposition may have an impact on EOS susceptibility and outcome. The aim of our study was to explore the association between TNF-α -308 G/A or IL-6 -174 G/C gene polymorphism and the susceptibility and outcome of EOS in preterm infants. The study included 471 preterm infants: 282 with EOS (151 with culture proven sepsis and 131 with clinical sepsis) and 189 without infection (control group). TNF-α -308 G/A and IL-6 -174 G/C were genotyped using Real-time RCR method. We observed significantly higher frequency of A allele of TNF-α -308 G/A polymorphism in blood culture proven EOS (p = 0.017) or clinical EOS (p = 0.025) compared with the control group. Logistic regression confirmed significant association between TNF-α -308 GA+AA genotypes and development of culture proven EOS (B = −0.718, p = 0.013) or clinical EOS (B = −0.602, p = 0.027). No significant differences in IL6 -174G/C alleles or genotypes distribution have been observed between culture proven EOS group, clinical EOS group and the control group. An association between TNF-α -308 G/A or IL-6 -174 G/C genotypes and EOS lethal outcome was not observed (p = 0.652 and p = 0.384, respectively). According to our analysis of large cohort of preterm infants with clearly defined EOS groups, the TNF-α -308 A allele may be a risk factor for the EOS occurrence.

keywords —— early onset sepsis; gene polymorphism; interleukin 6; preterm infants; tumor necrosis factor alpha

© 2019 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2019, 247, 259-264

Correspondence: Tatjana Damnjanovic, M.D., Ph.D., Institute of Human Genetics, Faculty of Medicine, University of Belgrade, 26 Visegradska Str., 11000 Belgrade, Serbia.

e-mail: tatjana.damnjanovic@med.bg.ac.rs