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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 kappa light polypeptide gene enhancer in B cells (IkappaBL), 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.

Original publication

DOI

10.1038/sj.gene.6364384

Type

Journal article

Journal

Genes and immunity

Publication Date

06/2007

Volume

8

Pages

288 - 295

Addresses

Clinical Research Unit, Infectious Tropical Disease Department, London School of Hygiene and Tropical Medicine, London University, Keppel Street, London, UK. angels.natividad-sancho@lshtm.ac.uk

Keywords

Cells, Cultured, Humans, Chlamydia trachomatis, Trachoma, Disease Progression, Genetic Predisposition to Disease, Tumor Necrosis Factors, Case-Control Studies, Haplotypes, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Gambia, Female, Male, Genetic Variation