The significance of polymorphisms in genes encoding Il-1β, Il-6, TNFα, and Il-1RN in the pathogenesis of intraventricular hemorrhage in preterm infants

Childs Nerv Syst. 2017 Nov;33(11):1905-1916. doi: 10.1007/s00381-017-3458-2. Epub 2017 Jun 29.

Abstract

Introduction: Intraventricular hemorrhage (IVH) is a significant morbidity seen in very low birth weight infants. Genes related to inflammation may be risk factors for IVH.

Material and methods: We examined five polymorphisms for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities. These polymorphisms include interleukin-1β 3953 C>T, interleukin-6 -174G>C and -596G>A, tumor necrosis factor -308 G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il -1RN 86 bp VNTR).

Results: In our study population, 45 (45%) infants developed IVH, including 15 (33.33%) with stage 1, 19 (42.22%) with stage 2, 8 (17.77%) with stage 3, and 3 (6.66%) with stage 4. In contrast to the previously published data, the prevalence of IVH did not vary between infants with different IL-6 and TNFα alleles and genotypes. Our novel investigations in Il-1 +3953 C>T and Il-1RN 86 bp VNTR polymorphism did not show any significant link between those alleles or genotypes and IVH.

Conclusions: IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that are focused on understanding the etiology, mechanism and risk factors for IVH are imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies. Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of IVH.

Keywords: Gene polymorphism; Intraventricular hemorrhage; Preterm neonates.

MeSH terms

  • Cerebral Intraventricular Hemorrhage / etiology
  • Cerebral Intraventricular Hemorrhage / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Male
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Premature Birth*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • IL6 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Interleukin-6
  • TNF protein, human
  • Tumor Necrosis Factor-alpha