Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population

Pediatr Res. 2002 Sep;52(3):373-6. doi: 10.1203/00006450-200209000-00011.


Premature birth causes significant health risks of the neonate and increases the cost for neonatal care. Urogenital infection, often caused by Gram-negative bacteria, is a known risk factor. Toll-like receptor-4 (TLR4) is the major endotoxin-signaling receptor and as such is crucial for the initiation of the innate immune response against Gram-negative bacteria. Recently, a variant in the human TLR4 gene was shown to be associated with impaired receptor function and an increased likelihood of Gram-negative sepsis. In the present study, we determined whether the same polymorphism in TLR4 gene is associated with an increased risk for premature birth. We analyzed genotypes for a Finnish study population consisting of a total of 351 term infants and 440 premature infants (gestational age <35 wk; 282 singletons, 158 multiples) and 94 mothers for the presence of the TLR4 polymorphisms Asp299Gly and Thr399Ile. These polymorphisms were in linkage disequilibrium. The 299Gly allele frequencies were 10.6% (93 of 880) in premature infants and 8.3% (58 of 72) in term infants. Excluding multiple pregnancies that often result in premature births, 23.8% (67 of 282) of premature infants and 24.2% (15 of 62) of the mothers of premature infants compared with 15.9% (55 of 345) of term infants and 15.0% (3 of 20) of the mothers delivering at term were carriers of the TLR4 variant. The frequencies of 299Gly allele and Asp/Gly or Gly/Gly genotype carrier status in premature singleton infants were higher than in term singleton infants (p = 0.024, p = 0.028, respectively) or in premature multiples (p = 0.036, p = 0.044, respectively). According to the present results an allelic variation in the TLR4 receptor was associated with increased risk of premature birth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aspartic Acid / metabolism*
  • Drosophila Proteins*
  • Endotoxins / metabolism
  • Female
  • Finland
  • Gene Frequency
  • Gestational Age
  • Glycine / metabolism*
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Membrane Glycoproteins / genetics*
  • Obstetric Labor, Premature / genetics*
  • Polymorphism, Genetic*
  • Pregnancy
  • Receptors, Cell Surface / genetics*
  • Risk Factors
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • Drosophila Proteins
  • Endotoxins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Aspartic Acid
  • Glycine