Variants in Toll-like Receptor 1 and 4 Genes Are Associated With Chlamydia trachomatis Among Women With Pelvic Inflammatory Disease (original) (raw)
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Drugs of today (Barcelona, Spain : 1998), 2009
Chlamydia trachomatis infections may cause several disease conditions ranging from asymptomatic infections to severe upper genital tract pathology, thereby causing significant morbidity worldwide. Remarkable interindividual differences in the clinical course of C. trachomatis infection have been observed, and are mainly based on variation in genes encoding immune-regulatory and bacteria-sensing proteins. Toll-like receptors (TLRs) are closely involved in pathogen recognition and host defense in C. trachomatis infections. The aim of this study is to assess the role of TLR2 single nucleotide polymorphisms and haplotypes in the susceptibility to, and severity of C. trachomatis infections. The study comprised a sexually transmitted disease cohort of 468 Dutch Caucasian women and a control group of 321 women. The subfertility cohort consisted of 56 women with clinically well-defined tubal pathology. The results showed no significant differences in individual TLR2 genotype frequencies in ...
Cytokine gene polymorphism and Chlamydia trachomatis-specific immune responses
Human Immunology, 2011
Chlamydia trachomatis-induced fallopian tube damage leading to tubal factor infertility (TFI) is linked with TNF, IL-10, and probably IFNG gene polymorphisms. The aim of this study was to clarify the contribution of these cytokine gene polymorphisms to interindividual variation in C trachomatis-specific immune responses and the cross-regulation of secreted cytokines and single nucleotide polymorphisms (SNPs). Cytokine polymorphisms (IL-10-1082A/G,-819T/C, and-592A/C, IFNG ϩ874T/A, and TNF-308G/A) were genotyped by polymerase chain reaction in 139 women. C trachomatis-specific immune responses were measured using lymphocyte proliferation (LP) induced by C trachomatis E and F strains and chlamydial heat shock protein 60 antigens. Cytokine secretion was measured in culture supernatants of infected and uninfected mononuclear leukocytes. IL-10-1082/-819/-592 and IFNG ϩ874 SNPs were associated with the intensity of LP responses to C trachomatis antigens. These cytokines also interact with each other and a cumulative effect of IL-10-1082 and IFNG ϩ874 genotypes was seen in LP responses to C trachomatis antigens. Our data suggest that interleukin-10 and interferon-␥ regulate C trachomatis-specific immune responses in humans and that genetic variation in the expression of their coding genes explains interindividual variation in host immune responses to C trachomatis infection.
Racial Variation in Toll-like Receptor Variants Among Women With Pelvic Inflammatory Disease
Journal of Infectious Diseases, 2013
Background. Racial disparities exist in gynecological diseases. Variations in Toll-like receptor (TLR) genes may alter signaling following microbial recognition. Methods. We explored genotypic differences in 6 functional variants in 4 TLR genes (TLR1, TLR2, TLR4, TLR6) and the adaptor molecule TIRAP between 205 African American women and 51 white women with clinically suspected pelvic inflammatory disease (PID). A permutated P < .007 was used to assess significance. Associations between race and endometritis and/or upper genital tract infection (UGTI) were explored. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results. The TT genotype for TLR1 rs5743618, the GG genotype for TLR1 rs4833095, the CC genotype for TLR2 rs3804099, the TLR6 rs5743810 T allele, and the CC genotype for TIRAP rs8177374 significantly differed between races (P < .007). African American race was associated with endometritis and/or UGTI (OR, 4.2 [95% CI, 2.0-8.7]; P = .01). Among African Americans, the TLR6 rs5743810 T allele significantly decreased endometritis and/or UGTI (OR, 0.4 [95% CI, .2-.9]; P = .04). Additionally, rs5743618, rs4833095, and rs8177374 increased endometritis and/or UGTI, albeit not significantly. Conclusions. Among women with PID, TLR variants that increase inflammation are associated with African American race and may mediate the relationship between race and endometritis and/or UGTI.
BMC infectious diseases, 2005
The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women. The different CD14 -260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology stat...
Drugs of today (Barcelona, Spain : 1998), 2009
Susceptibility to Chlamydia trachomatis infections is 40% host based. microRNA-146a is a negative regulator of Tolllike receptor (TLR) signaling and possesses functional polymorphisms which decrease the production of premiR-146a and mature miR-146a. Single nucleotide polymorphisms (SNPs) in NLRP3 are associated with decreased NLRP3 expression and hypoproduction of interleukin (IL)-1beta. We investigated whether the SNPs miR-146a G>C (rs2910164), NLRP3 C>T (rs4925663) and G>A (rs12065526) are associated with the susceptibility to and severity of C. trachomatis infection. The genotypes of three SNPs were tested in two cohorts: cohort 1 consists of Dutch women (n = 318) attending a sexually transmitted disease (STD) clinic and cohort 2 (n = 277) consists of subfertile (n = 184) and healthy Finnish women (n=93). While in cohort 1 the analyzed SNPs were not associated with the susceptibility to C. trachomatis infections (C. trachomatis-positive vs. C. trachomatis-negative), we s...
Drugs of today (Barcelona, Spain : 1998), 2009
Chlamydia trachomatis is the most prevalent sexually transmitted bacterium in the world with almost 100 million new cases each year, some of which will develop tubal pathology. Clear differences in its clinical course of infections have been observed, and recently it has been shown that 40% is based on host genetic factors. We used an integrated approach based on infection of Toll-like receptor 4 (TLR4) knockout mice and immunogenetic analysis of female sexually transmitted disease (STD) patients (susceptibility) and women with C. trachomatis-associated tubal factor subfertility (severity). The results in TLR4 knockout mice suggest that the protection against reinfection is more solid in normal as compared to the TLR4-deficient mice. In humans the functional TLR4 single nucleotide polymorphism studied was not involved in the susceptibility to infection. However, C. trachomatis immunoglobulin (Ig) G-positive subfertile women with tubal pathology were more than twice as likely to be c...
Sexually Transmitted Infections, 2013
Objective Most women with Chlamydia trachomatis (CT) infection are asymptomatic, while ~3% progress to pelvic inflammatory disease (PID) within two weeks of untreated infection. The identification of biomarkers that predict development of PID would aid in identification of women at risk for complications of infertility and ectopic pregnancy. The specific aim of this study was to identify a whole blood transcript signature for acute PID due to chlamydial infection. Methods We performed gene expression microarrays using whole blood from 79 women who had a gynecologic exam, and cervical and endometrial microbiologic testing.
BMC Infectious …, 2005
Background: The functional polymorphism-260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14-260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women. Methods: The different CD14-260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology status and the tubal status at laparoscopy. Results: In the control cohort the CC, CT and TT genotype distribution was: 28.2%, 48.2%, and 23.5% respectively. No differences were found in the overall prevalence of CD14-260 genotypes (28.1%, 50.7%, and 21.2%) in cohort 1 when compared to the control cohort. Also no differences were observed in women with or without CT-DNA, with or without serological CT responses, with or without symptoms, or in combinations of these three variables. In subfertile women with tubal pathology (cohort 2, n = 50) the genotype distribution was 28.0%, 48.0%, and 24.0% and in subfertile women without tubal pathology (n = 203), 27.6%, 49.3% and 23.2%. The genotype distribution was unchanged when CT IgG status was introduced in the analyses. Conclusion: The CD14-260 C>T genotype distributions were identical in all three cohorts, showing that this polymorphism is not involved in the susceptibility to or severity of sequelae of C. trachomatis infection.
Molecular Diagnosis of Genital Chlamydia trachomatis in Women with Pelvic Inflammatory Disease
RJPBCS, 2016
Frequency of STI infections has a low rate in Muslim and Arabic societies due to injunction and ethics to prevent non-marital sex and sexual promiscuity. In Iraq, there has been very little surveillance program to screen C. trachomatis infection, thus this research aimed to detect frequency of genital chlamydia in female with PID via genetic diagnosis of C. trachomatis by the use of 16S rDNA and 16S-23S rDNA spacer and comparison between them. This study included 232 endocervical swab samples collected from female patients suffering from signs and/or symptoms of PID; and were diagnosed as having PID by the gynecologist and had risk factors for this infection. These swabs were subjected to DNA extraction, and further processing by polymerase chain reaction. Using 16S rRNA and 16S-23S rRNA spacer genes as genetic markers via conventional PCR; both of them gave approximate results 7/232 (3.02%) versus 8/232 (3.45%) respectively. The highest frequency distribution 4/8 (50%) of C. trachomatis among the age group of 20-40 years, while 2/8 (25%) from both age group less than 20 years, and more than 40 years separately. While association with the use of different types of contraceptives; 50% of chlamydial positive patients used oral contraceptive pills during their life. While those using intrauterine contraceptive devices representing 25%, and remaining cases represented 12.5% used barrier methods and 12.5% did not use any type. The study concluded that 16S rRNA and 16S-23S rRNA spacer genes are considered as sensitive and specific methods for the identification of C. trachomatis in women.