title: TLR2, TLR4 and TLR9 genotypes and haplotypes in the susceptibility to and clinical course of Chlamydia trachomatis infections in Dutch women.
abstract: Chlamydia trachomatis infections demonstrate remarkable differences in clinical course that are approximately 40% based on host genetic variation. Here, we study the single nucleotide polymorphisms (SNPs) and their haplotypes in TLR2, TLR4 and TLR9 (TLR2 +2477G>A; TLR2 -16934T>A; TLR4+896A>G; TLR9 -1237T>C and TLR9 +2848G>A) in relation to the susceptibility to, and severity of C. trachomatis infections. We analysed the five SNPs in a cohort of 770 Dutch Caucasian women either attending a sexually transmitted diseases outpatient clinic (n = 731) or having complaints of subfertility (n = 39). Haplotype analyses showed a trend for TLR2 haplotype I (-16934T/+2477G) to protect against the development of symptoms and tubal pathology (Ptrend = 0.03) after Chlamydia infection. In the susceptibility cohort, TLR9 haplotype III (-1237C/+2848A) showed a significant decreasing trend in the development of symptoms after C. trachomatis infection (P = 0.02, OR: 0.55, 95%CI: 0.33-0.91). Logistic regression of the TLR2 haplotypes, TLR4+896A>G, and TLR9 haplotypes showed that the TLR2 haplotype combinations AG-TA and AG-TG confer risk (OR 3.4 (P = 0.01) and 1.6 (P = 0.03)), while the TLR9 haplotype combination TG-TA protects against C. trachomatis infections (OR: 0.4, P = 0.004). Our study shows that both TLR2 and TLR9 genes and SNP combinations do influence the clinical course of Chlamydia infections.
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, 1081 HV, the Netherlands.
authors.forename: Stephan P
authors.initials: SP
authors.lastname: Verweij
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, 1081 HV, the Netherlands Department of Internal Medicine, VU University Medical Center, Amsterdam, 1081 HV, the Netherlands.
authors.forename: Ouafae
authors.initials: O
authors.lastname: Karimi
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, 1081 HV, the Netherlands.
authors.forename: Jolein
authors.initials: J
authors.lastname: Pleijster
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, 1081 HV, the Netherlands.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lyons
authors.affiliation: STI outpatient clinic, Cluster Infectious Diseases, Municipal Health Service Amsterdam, Amsterdam, 1018 WT, the Netherlands Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, 1105 AZ, the Netherlands National Institute for Public Health and the Environment, Bilthoven, 3721 MA, the Netherlands Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands.
authors.forename: Henry J C
authors.initials: HJ
authors.lastname: de Vries
authors.affiliation: Department of Obstetrics and Gynaecology, UMCG, University of Groningen, Groningen, 9713 GZ, the Netherlands.
authors.forename: Jolande A
authors.initials: JA
authors.lastname: Land
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, 1081 HV, the Netherlands Institute of Public Health Genomics, Department of Genetics and Cell Biology, Research Institute GROW, Faculty of Health, Medicine & Life Sciences, University of Maastricht, Maastricht, 6229 ER, the Netherlands samorretravel@yahoo.co.uk.
authors.forename: Servaas A
authors.initials: SA
authors.lastname: Morré
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, 1081 HV, the Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Ouburg
mesh_terms: D000293:Adolescent; D000328:Adult; D002692:Chlamydia trachomatis / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008219:Lymphogranuloma Venereum / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D044465:White People; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9
keywords: Chlamydia trachomatis; Clinical outcome; Immunogenetics; Toll-like receptors