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.
Lorenz
Eva
E
Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. elorenz@wfubmc.edu
Hallman
Mikko
M
Marttila
Riitta
R
Haataja
Ritva
R
Schwartz
David A
DA
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