Pathway-Wide Genetic Risks in Chlamydial Infections Overlap between Tissue Tropisms: A Genome-Wide Association Scan

Chrissy H Roberts,Martin J Holland,Sander Ouburg,Mark D Preston,Henry J C De Vries,Servaas A Morré

doi:10.1155/2018/3434101

Abstract

Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection and can lead to tubal factor infertility, a disease characterised by fibrosis of the fallopian tubes. Genetic polymorphisms in molecular pathways involving G protein-coupled receptor signalling, the Akt/PI3K cascade, the mitotic cell cycle, and immune response have been identified in association with the development of trachomatous scarring, an ocular form of chlamydia-related fibrotic pathology. In this case-control study, we performed genome-wide association and pathways-based analysis in a sample of 71 Dutch women who attended an STI clinic who were seropositive for Chlamydia trachomatis antibodies and 169 high-risk Dutch women who sought similar health services but who were seronegative. We identified two regions of within-gene SNP association with Chlamydia trachomatis serological response and found that GPCR signalling and cell cycle pathways were also associated with the trait. These pathway-level associations appear to be common to immunological sequelae of chlamydial infections in both ocular and urogenital tropisms. These pathways may be central mediators of human refractoriness to chlamydial diseases.

Highlights

Chlamydia trachomatis (Ct) is diagnosed as the cause of around 106 million sexually transmitted infections (STIs) per annum [1] and has a significant impact on global health.The primary pathology associated with Ct infection is an aberrant host immune response [2] which can lead to the progressive formation of scar tissues at and near the site of infection [3,4,5]
This is largely due to the relative ease with which the conjunctiva can be studied compared to Mediators of Inflammation the fallopian tubes and because of the high prevalence of trachomatous scarring in sub-Saharan Africa [8, 9] compared to Ct pathology [10] in Europe and elsewhere
One of these genomic regions of association was within the protein kinase, CGMP-dependent, type I gene (PRKG1) whilst another was within NPSR1 antisense RNA 1 (NPSR1-AS1), which presumably has a role in posttranscriptional control of the nearby gene neuropeptide S receptor 1 (NPSR1)

Summary

Introduction

Chlamydia trachomatis (Ct) is diagnosed as the cause of around 106 million sexually transmitted infections (STIs) per annum [1] and has a significant impact on global health.The primary pathology associated with Ct infection is an aberrant host immune response [2] which can lead to the progressive formation of scar tissues at and near the site of infection [3,4,5]. Chlamydia trachomatis (Ct) is diagnosed as the cause of around 106 million sexually transmitted infections (STIs) per annum [1] and has a significant impact on global health. In the context of STIs, this process can lead to infection-related tubal factor infertility (TFI) and ectopic pregnancy [6]. Trachoma has historically been used as a platform for the study of chlamydial diseases and their pathology. This is largely due to the relative ease with which the conjunctiva can be studied compared to Mediators of Inflammation the fallopian tubes and because of the high prevalence of trachomatous scarring in sub-Saharan Africa [8, 9] compared to Ct pathology [10] in Europe and elsewhere

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