Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population.
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.
Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. elorenz@wfubmc.edu
Eva
E
Lorenz
Mikko
M
Hallman
Riitta
R
Marttila
Ritva
R
Haataja
David A
DA
Schwartz
D001224:Aspartic Acid / Q000378:metabolism*; D029721:Drosophila Proteins; D004731:Endotoxins / Q000378:metabolism; D005260:Female; D005387:Finland; D005787:Gene Frequency; D005865:Gestational Age; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008562:Membrane Glycoproteins / Q000235:genetics*; D007752:Obstetric Labor, Premature / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics*; D012307:Risk Factors; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D004731:Endotoxins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D001224:Aspartic Acid; D005998:Glycine