Łukaszewski Tomasz, Barlik Magdalena, Seremak-Mrozikiewicz Agnieszka, Kurzawińska Grazyna, Mrozikiewicz Przemysław M, Sieroszewski Piotr, Drews Krzysztof
Klinika Perinatologii i Chorób Kobiecych, Uniwersytet Medyczny w Poznaniu.
Ginekol Pol. 2009 Dec;80(12):914-9.
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.
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.
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.
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.
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.
Toll样受体(TLR)-2和-4是抵御细菌感染的基本防御机制的一部分。它们识别微生物产物并增强宿主生物体的免疫反应。TLR受体的表达与羊膜腔内感染(IAI)以及早产之间的关系已得到证实。因此,有人认为TLR-2和-4基因多态性、胎膜早破(PROM)、羊膜腔内感染和早产之间存在关联。
以下研究的目的是评估一组胎膜早破和早产孕妇中TLR-2基因的Arg753Gln(G20877A)和TLR-4基因的Thr399Ile(C8993T)这两种基因多态性的频率。
33例诊断为妊娠30至36周胎膜早破的孕妇(研究组)和60例健康孕妇(对照组)纳入研究。采用聚合酶链反应和限制性片段长度多态性(PCR/RFLP)分析TLR-2基因的Arg753Gln多态性和TLR-4基因的Thr399Ile多态性。
对于TLR-2基因的G20877A多态性,研究组杂合子GA基因型的频率为9.1%,与对照组(8.3%,p=无统计学意义)相当。此外,两个检测组中突变的G等位基因频率相当(研究组为4.6%,对照组为4.2%,p=无统计学意义)。对于TLR-4基因的C8993T多态性,研究组杂合子CT基因型的频率低于对照组(9.1%对16.7%)。研究组纯合子CC基因型的频率更高(90.0%对83.3%,p=无统计学意义),优势比(OR)相对较高(OR=2.0)。通过分析两个检测组中等位基因的频率也得到了类似的观察结果。
对照组中TLR-4基因C8993T多态性的杂合子CT基因型和突变的T等位基因的过度表达可能表明,它可能对胎膜早破起到保护作用。然而,这一假设需要在更大规模的胎膜早破患者群体中进一步研究。