[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].
BACKGROUND
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.


OBJECTIVE
The aim of the following study was to evaluate the frequency of two genetic polymorphisms: Arg753Gln (G20877A) in TLR-2 and Thr399lle (C8993T) in TLR-4 genes in a group of pregnant women with preterm rupture of membranes and preterm labour.


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 Thr399lle 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.


CONCLUSIONS
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.
Łukaszewski
Tomasz
T
Klinika Perinatologii i Chorób Kobiecych, Uniwersytet Medyczny w Poznaniu. lukaszewski_tomasz@o2.pl
Barlik
Magdalena
M
Seremak-Mrozikiewicz
Agnieszka
A
Kurzawińska
Grazyna
G
Mrozikiewicz
Przemysław M
PM
Sieroszewski
Piotr
P
Drews
Krzysztof
K
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics*; D006801:Humans; D007752:Obstetric Labor, Premature / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4