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Mol. Hum. Reprod. Advance Access published online on October 29, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah120
© 2004 by Oxford University Press
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Received June 15, 2004
Revised September 24, 2004
Accepted October 3, 2004

Article

Polymorphisms of genes involved in innate immunity: association with preterm delivery

Ch. Härtel 1, D. Finas 2, P. Ahrens 1, E. Kattner 3, Th. Schaible 4, D. Müller 5, H. Segerer 6, K. Albrecht 7, J. Möller 8, K. Diedrich 2, W. Göpel 1*, and for the Genetic Factors in Neonatology Study Group

1 Department of Pediatrics, University of Luebeck, Childrens Hospital auf der Bult, Hannover, Germany
2 Department of Obstetrics and Gynecology, University of Luebeck, Childrens Hospital auf der Bult, Hannover, Germany
3 Childrens Hospital auf der Bult, Hannover, Germany
4 University Childrens Hospital, Mannheim, Germany
5 Childrens Hospital Kassel, Germany
6 Childrens Hospital St. Hedwig, Regensburg, Germany
7 Childrens Hospital St. Jürgen-Straße, Bremen, Germany
8 Childrens Hospital Saarbrücken, Germany

* To whom correspondence should be addressed.
W. Göpel, E-mail: goepel{at}paedia.ukl.mu-luebeck.de


  Abstract

An altered inflammatory activity due to functionally relevant polymorphisms of the innate immune system may influence pathways leading to labour and, therefore, impact on the frequency of preterm birth. We examined five polymorphisms of the innate immune system in a large cohort of preterm very-low-birth-weight (VLBW, n=909) and term-born infants (n=491) and their mothers (n=747). The primary outcome was preterm versus term birth. Frequencies of polymorphisms in mothers of term-born infants versus mothers of VLBW infants and term infants versus preterm VLBW infants (singletons) are given. Homozygous CD14-159T: 18.5 versus 21.8% (mothers) and 19.6 versus 21.2% (infants). Homozygous interleukin IL-6-174G: 28.8 versus 38% (P=0.018, mothers) and 30 versus 32.7% (infants). Homozygous or heterozygous nuclear oligomerization domain NOD2-3020insC: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Heterozygous or homozygous toll-like-receptor TLR2-Arg753Gln: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Homozygous or heterozygous TLR4-896G: 8.1 versus 11.5% (mothers) and 11.6 versus 10.5% (infants). Although the homozygous maternal IL-6-174G genotype was found to be independently associated with preterm delivery in multivariate regression analysis, the incidence of intrauterine infection was not significantly increased in mothers of preterm VLBW-infants, carrying this or other polymorphisms of the innate immune system. The overall influence of the investigated polymorphisms on the development of preterm delivery seems moderate, since only the maternal IL6-174G genotype was associated with preterm birth and none of the polymorphisms were associated with intrauterine infection as the cause of preterm birth.

Keywords: innate immunity; interleukin; intrauterine infection; preterm delivery; toll-like receptor.
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