Replication of genetic associations in the inflammation, complement, and coagulation pathways with intraventricular hemorrhage in LBW preterm neonates

Pediatr Res. 2011 Jul;70(1):90-5. doi: 10.1203/PDR.0b013e31821ceb63.

Abstract

Intraventricular hemorrhage (IVH) is a significant morbidity seen in very LBW infants. Genes related to the inflammation, infection, complement, or coagulation pathways have been implicated as risk factors for IVH. We examined 10 candidate genes for associations with IVH in 271 preterm infants (64 with IVH grades I-IV and 207 without IVH) weighing <1500 g. The heterozygous genotype OR = 8.1, CI = 2.5-26.0, p = 4 × 10(-4)) and the A allele (OR = 7.3, CI = 2.4-22.5, p = 1 × 10(-4)) of the coagulation factor V (FV) Leiden mutation (rs6025) were associated with an increased risk of developing IVH grade I or II but not grade III or IV after correction for multiple testing with Bonferroni. Lack of association in the severe grades of IVH may be a result of lack of power to detect an effect given the small sample size (n = 8). However, this result is consistent with previous research that demonstrates that the heterozygous genotype of the FV mutation is associated with increased risk for the development of IVH but a decreased risk for the progression or extension to more severe grades of IVH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation / genetics*
  • Complement System Proteins / genetics*
  • Cytokines / genetics
  • Estrogen Receptor alpha / genetics
  • Factor V / genetics
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Gestational Age
  • Heterozygote
  • Humans
  • Infant, Low Birth Weight*
  • Infant, Newborn
  • Infant, Premature*
  • Inflammation / blood
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation Mediators / metabolism
  • Integrin beta3 / genetics
  • Intracranial Hemorrhages / blood
  • Intracranial Hemorrhages / genetics*
  • Intracranial Hemorrhages / immunology
  • Iowa
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index

Substances

  • Cytokines
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • ITGB3 protein, human
  • Inflammation Mediators
  • Integrin beta3
  • factor V Leiden
  • Factor V
  • Complement System Proteins