Vol 80, No 12 (2009)

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Polymorphism in the genes of Toll-like receptors type 2 and type 4 (TLR-2 and TLR-4) and the risk of premature rupture of the membranes – preliminary study

Krzysztof Drews, Piotr Sieroszewski, Przemysław M. Mrozikiewicz, Grażyna Kurzawińska, Magdalena Barlik, Agnieszka Seremak-Mrozikiewicz, Tomasz Łukaszewski
Ginekol Pol 2009;80(12).


Introduction: Toll-like receptors (TLR) -2 and -4 are a part of basic defence mechanism protecting against bacterial infections. They recognize microbial products and increase immune response of the host organism. The relationship between the expression of TLR receptors and the occurrence of intraamniotic infection (IAI) as well as preterm labour was demonstrated. Therefore, a relationship between TLR-2 and -4 genes polymorphism, premature rupture of membranes (PROM), intraamniotic infection and preterm labour is claimed to exist. Aim: The aim of the following study was to evaluate the frequency of two genetic polymorphisms: Arg753Gln (G20877A) in TLR-2 and Thr399Ile (C8993T) in TLR-4 genes in a group of pregnant women with preterm rupture of membranes and preterm labour. Material and methods: 33 pregnant women with the diagnosis of preterm – between 30 and 36 weeks of gestation – rupture of membranes (study group), and 60 healthy pregnant women (controls) were enrolled into the study. To analyse Arg753Gln polymorphism of TLR-2 gene and Thr399Ile polymorphism of TLR-4 gene, polymerase chain reaction and restriction fragments length polymorphism (PCR/RFLP) were used. Results: For G20877A polymorphism in TLR-2 gene, the frequency of heterozygous GA genotype in the study group was 9.1% and was comparable with the control group (8.3%, p=ns). Moreover, frequency mutated G allele was comparable in both examined groups (4.6% in the study group and 4.2% in the control group, p=ns). For C8993T polymorphism in TLR-4 gene, heterozygous CT genotype was less frequent in the study group in comparison with the control group (9.1 vs. 16.7%). The homozygous CC genotype was more frequent in the study group (90.0 vs 83.3%, p=ns), with relatively high value of the odds ratio (OR=2,0). Similar observations were conducted by analysing the frequencies of the alleles in both examined groups. Conclusion: Overrepresentation of heterozygous CT genotype and mutated T allele of C8993T polymorphism in TLR-4 gene in the control group may indicate that, possibly, it plays a protective role against PROM. However, this hypothesis requires further investigation on a larger group of patients with premature rupture of membranes.

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