Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?

Janneke E Den Hartog,Jolande A Land,A Salvador Peña,Joseph M Lyons,James I Ito,Servaas A Morré,Sander Ouburg

doi:10.1186/1471-2334-6-122

Abstract

BackgroundIn 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.MethodsOf 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.ResultsFollowing 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.ConclusionCarrying 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.

Highlights

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
The genotype distribution did not differ between subfertile women, the C. trachomatis IgG-positive subgroup of subfertile women and the healthy control group (Table 2), indicating that the subfertile women participating in the study reflect an average Dutch Caucasian population regarding the genotype distribution
Single gene analysis The risk of tubal pathology was assessed in all subfertile women and in the C. trachomatis IgG-positive subgroup in relation to the genotype of TLR9, TLR4, CD14 and

Summary

Introduction

Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Immunogenetic studies evaluate the role of genetic variations in immunologically important host genes as determinants of the susceptibility, course and outcome of infectious diseases. Among these variations are single nucleotide polymorphisms (SNPs), in which one nucleotide has been substituted, inserted or deleted. This may lead to synthesis of a potentially aberrant protein, or to up- or downregulation of the normal protein, and subsequently to an aberrant immune response, increasing the risk of late sequelae of infectious diseases (e.g. tubal pathology following a C. trachomatis infection)

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