[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].

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 Thr399lle (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 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. 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.

[1]  P. Aghajanian.  Preterm Premature Rupture of the Membranes , 2010 .

[2]  B. Vincenzi,et al.  Toll‐like receptor 4 Asp299Gly and Thr399Ile polymorphisms in gastric cancer of intestinal and diffuse histotypes , 2008, Clinical and experimental immunology.

[3]  S. Nejentsev,et al.  Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis , 2008, PLoS genetics.

[4]  J. Hampe,et al.  Study of Toll‐like receptor gene loci in sarcoidosis , 2008, Clinical and experimental immunology.

[5]  P. Rahman,et al.  Analysis of single nucleotide polymorphisms in Toll-like receptor 4 shows no association with ankylosing spondylitis in a Korean population , 2008, Rheumatology International.

[6]  T. Merriman,et al.  TLR2, TLR4 and TLR9 polymorphisms and Crohn's disease in a New Zealand Caucasian cohort , 2007, Journal of gastroenterology and hepatology.

[7]  U. Ghoshal,et al.  Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. , 2007, Human immunology.

[8]  P. Sly,et al.  TLR4 Polymorphisms Mediate Impaired Responses to Respiratory Syncytial Virus and Lipopolysaccharide1 , 2007, The Journal of Immunology.

[9]  N. Kutukculer,et al.  Arg753Gln Polymorphism of the Human Toll-like Receptor-2 Gene in Children with Recurrent Febrile Infections , 2007, Biochemical Genetics.

[10]  A. Gillissen,et al.  Toll‐like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis , 2006, Clinical and experimental immunology.

[11]  M. Klebanoff,et al.  Differences in inflammatory cytokine and Toll-like receptor genes and bacterial vaginosis in pregnancy. , 2005, American journal of obstetrics and gynecology.

[12]  S. Saito,et al.  Toll-like receptor 4: a potential link between "danger signals," the innate immune system, and preeclampsia? , 2005, American journal of obstetrics and gynecology.

[13]  G. Mor,et al.  Toll-like receptors and their role in the trophoblast. , 2005, Placenta.

[14]  H. Çelik,et al.  TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children , 2005, Journal of Molecular Medicine.

[15]  N. Lurain,et al.  Induction of tumor necrosis factor- alpha secretion and toll-like receptor 2 and 4 mRNA expression by genital mucosal fluids from women with bacterial vaginosis. , 2005, The Journal of infectious diseases.

[16]  B. Mercer.  Preterm premature rupture of the membranes: diagnosis and management. , 2004, Clinics in perinatology.

[17]  E. Norwitz,et al.  Relationship between a toll-like receptor-4 gene polymorphism, bacterial vaginosis-related flora and vaginal cytokine responses in pregnant women. , 2004, European journal of obstetrics, gynecology, and reproductive biology.

[18]  G. Mor,et al.  Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis. , 2004, American journal of obstetrics and gynecology.

[19]  T. Mussack,et al.  Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. , 2004, Clinical immunology.

[20]  R. Goldenberg,et al.  Infection as a cause of preterm birth. , 2003, Clinics in perinatology.

[21]  M. Góralski,et al.  Rola receptorow Toll-podobnych w odpornosci , 2004 .