Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study.


Roberts, CH; Franklin, CS; Makalo, P; Joof, H; Sarr, I; Mahdi, OS; Sillah, A; Bah, M; Payne, F; Jeffreys, AE; Bottomley, W; Natividad, A; Molina-Gonzalez, S; Burr, SE; Preston, M; Kwiatkowski, D; Rockett, KA; Clark, TG; Burton, MJ; Mabey, DC; Bailey, R; Barroso, I; Holland, MJ; (2015) Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study. Sci Rep, 5. p. 17447. ISSN 2045-2322 DOI: 10.1038/srep17447

[img] Text - Published Version
License:

Download (1177Kb)

Abstract

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10(-6) > P > 5 × 10(-8)). The most strongly associated SNP (rs111513399, P = 5.38 × 10(-7)) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Neglected Tropical Diseases Network
PubMed ID: 26616738
Web of Science ID: 365419000001
URI: http://researchonline.lshtm.ac.uk/id/eprint/2373989

Statistics


Download activity - last 12 months
Downloads since deposit
139Downloads
198Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item