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Mol. Hum. Reprod. Advance Access published online on August 22, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan049
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Toll Receptor 4 Asp299Gly Polymorphism and its association with Preterm Birth and Premature Rupture of Membranes in a South American population

G. Rey1, F. Skowronek1, J. Alciaturi1, J. Alonso2, B. Bertoni3 and R. Sapiro1,4

1Laboratory of Molecular Biology of Reproduction-Department of Histology and Embryology, School of Medicine 2Department of Obstetrics and Gynecology C Pereira Rossell Hospital 3Department of Genetics. University of Uruguay, School of Medicine. Montevideo, Uruguay

4 To whom correspondence should be addressed at: Laboratory of Molecular Biology of Reproduction-Department of Histology and Embryology, School of Medicine, Gral. Flores 2125, CP 11800, Montevideo, Uruguay. Tel: +598 2924 3414 ext 3551. E-mail: rsapiro{at}fmed.edu.uy

Preterm birth is a worldwide health problem and remains the leading cause of perinatal morbidity and mortality. Systemic and local intrauterine infections have been implicated in the pathogenesis of preterm labor and delivery. Common pathways between preterm birth, premature rupture of ovular membranes (PROM) and altered molecular routes of inflammation have been proposed. There is evidence to support a genetic component in these conditions. Lipopolysaccharide (LPS), a component of the cell wall of Gram negative bacteria, is thought to play a key role in eliciting an inflammatory response. LPS is recognized by proteins of the innate immune system, including Toll-like receptor 4 (TLR4). Individuals from some Europeans countries carrying the variant alleles resulting in an amino acid substitution (Asp299Gly) are at increased risk of Gram-negative infections and premature birth. The objective of this study was to determine if preterm newborns have different allele frequency of the Asp299Gly TLR4 variant than healthy term neonates in Uruguay. The impact of PROM was also examined. There was an increase in the risk for fetuses carrying the Asp299Gly substitution in TLR4 of being severely premature (less than 33 weeks) and to present PROM at the same time.

Key Words: TLR4 polymorphism/preterm birth/premature rupture of membranes/genetic association/South American population

Submitted on December 27, 2008; resubmitted on August 8, 2008; accepted on August 12, 2008.


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