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

Chrissy H. Roberts*, Sander Ouburg, Mark D. Preston, Henry J. C. de Vries, Martin J. Holland, Servaas A. Morre

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Article number3434101
Pages (from-to)1-9
Number of pages9
JournalMediators of Inflammation
Volume2018
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • TRACHOMATIS INFECTION
  • SCARRING TRACHOMA
  • HISTOPATHOLOGY
  • SUSCEPTIBILITY
  • IMPUTATION
  • MECHANISM
  • COMPONENT
  • ASSAY
  • Humans
  • Risk Factors
  • Genotype
  • Case-Control Studies
  • Chlamydia Infections/genetics
  • Chlamydia trachomatis/pathogenicity
  • Young Adult
  • Receptors, G-Protein-Coupled/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Genome-Wide Association Study/methods
  • Adolescent
  • Adult
  • Female
  • In Vitro Techniques

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