1. ¹Clinical Research Unit, Infectious Tropical Disease Department, London School of Hygiene and Tropical Medicine, London University, London, UK
2. ²Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
3. ³Medical Research Council Laboratories, Fajara, The Gambia
4. ⁴The National Eye Care Program, Banjul, The Gambia

Correspondence: Dr A Natividad, Clinical Research Unit, Infectious Tropical Disease Department, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. E-mail: angels.natividad-sancho@lshtm.ac.uk

⁵Current address: University of Tennessee, Health Science Center, Memphis, TN, USA

Received 15 November 2006; Revised 26 January 2007; Accepted 30 January 2007; Published online 1 March 2007.

Abstract

Tumor necrosis factor (TNF) is thought to be a key mediator of the inflammatory and fibrotic response to Chlamydia trachomatis (Ct) infection. A large matched-pair case–control study investigated putative functional single nucleotide polymorphisms (SNPs) across the major histocompatibility complex (MHC) class III region, including TNF and its immediate neighbors nuclear factor of light polypeptide gene enhancer in B cells (IBL), inhibitor like 1 and lymphotoxin alpha (LTA) in relation to the risk of scarring sequelae of ocular Ct infection. Haplotype and linkage disequilibrium analysis demonstrated two haplotypes, differing at position TNF-308, conferring an increased risk of trichiasis. The TNF-308A allele, and its bearing haplotype, correlated with increased TNF production in lymphocyte cultures stimulated with chlamydial elementary body antigen. Thus TNF-308A may determine directly, or be a marker of a high TNF producer phenotype associated with increased risk of sequelae of chlamydial infection. Multivariate analysis provided evidence for the presence of additional risk-associated variants near the TNF locus.