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Open Access Highly Accessed Research article

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 Hartog1*, Sander Ouburg2, Jolande A Land16, Joseph M Lyons36, James I Ito36, A Salvador Peña26 and Servaas A Morré2456

Author Affiliations

1 Research Institute Growth and Development (GROW) and Department of Obstetrics and Gynaecology, Academic Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands

2 Laboratory of Immunogenetics, Section Immunogenetics of Infectious Diseases, Department of Pathology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands

3 Department of Infectious Diseases, City of Hope National Medical Center and Beckman Research Institute, 1500 E. Duarte Road, Duarte, California 91010, USA

4 Department of Internal Medicine, Section Infectious Diseases, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands

5 Department of Medical Microbiology, Academic Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands

6 On behalf of the ICTI consortium (Integrated approach to the study of Chlamydia trachomatis Infections) and the EpiGenChlamydia consortium

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BMC Infectious Diseases 2006, 6:122  doi:10.1186/1471-2334-6-122

Published: 21 July 2006

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.

Conclusion

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.