title: Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?
abstract: BACKGROUND
  In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Variations, like single nucleotide polymorphisms (SNPs), in immunologically important host genes are assumed to play a role in the course and outcome of a C. trachomatis infection. We studied whether genetic traits (carrying multiple SNPs in different genes) in the bacterial sensing system are associated with an aberrant immune response and subsequently with tubal pathology following a C. trachomatis infection. The genes studied all encode for pattern recognition receptors (PRRs) involved in sensing bacterial components.
  
  
  METHODS
  Of 227 subfertile women, serum was available for C. trachomatis IgG antibody testing and genotyping (common versus rare allele) of the PRR genes TLR9, TLR4, CD14 and CARD15/NOD2. In all women, a laparoscopy was performed to assess the grade of tubal pathology. Tubal pathology was defined as extensive peri-adnexal adhesions and/or distal occlusion of at least one tube.
  
  
  RESULTS
  Following a C. trachomatis infection (i.e. C. trachomatis IgG positive), subfertile women carrying two or more SNPs in C. trachomatis PRR genes were at increased risk of tubal pathology compared to women carrying less than two SNPs (73% vs 33% risk). The differences were not statistically significant (P = 0.15), but a trend was observed.
  
  
  CONCLUSIONS
  Carrying multiple SNPs in C. trachomatis PRR genes tends to result in an aberrant immune response and a higher risk of tubal pathology following a C. trachomatis infection. Larger studies are needed to confirm our preliminary findings.
authors.affiliation: Research Institute Growth and Development (GROW) and Department of Obstetrics and Gynaecology, Academic Hospital Maastricht, P,O, Box 5800, 6202 AZ Maastricht, The Netherlands. je_denhartog@hotmail.com
authors.forename: Janneke E
authors.initials: JE
authors.lastname: den Hartog
authors.forename: Sander
authors.initials: S
authors.lastname: Ouburg
authors.forename: Jolande A
authors.initials: JA
authors.lastname: Land
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lyons
authors.forename: James I
authors.initials: JI
authors.lastname: Ito
authors.forename: A Salvador
authors.initials: AS
authors.lastname: Peña
authors.forename: Servaas A
authors.initials: SA
authors.lastname: Morré
mesh_terms: D000907:Antibodies, Bacterial / Q000302:isolation & purification; D002690:Chlamydia Infections / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D002692:Chlamydia trachomatis / Q000472:pathogenicity / Q000502:physiology*; D005187:Fallopian Tubes / Q000382:microbiology / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D007247:Infertility, Female / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein; D020641:Polymorphism, Single Nucleotide; D012488:Salpingitis / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9