title: Genetic variation at the TNF locus and the risk of severe sequelae of ocular Chlamydia trachomatis infection in Gambians.
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 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.
authors.affiliation: 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
authors.forename: A
authors.initials: A
authors.lastname: Natividad
authors.forename: N
authors.initials: N
authors.lastname: Hanchard
authors.forename: M J
authors.initials: MJ
authors.lastname: Holland
authors.forename: O S M
authors.initials: OS
authors.lastname: Mahdi
authors.forename: M
authors.initials: M
authors.lastname: Diakite
authors.forename: K
authors.initials: K
authors.lastname: Rockett
authors.forename: O
authors.initials: O
authors.lastname: Jallow
authors.forename: H M
authors.initials: HM
authors.lastname: Joof
authors.forename: D P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.forename: D C W
authors.initials: DC
authors.lastname: Mabey
authors.forename: R L
authors.initials: RL
authors.lastname: Bailey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002692:Chlamydia trachomatis / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005714:Gambia; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014141:Trachoma / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D048069:Tumor Necrosis Factors / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D048069:Tumor Necrosis Factors