Natividad A, Hanchard N, Holland M J, Mahdi O S M, Diakite M, Rockett K, Jallow O, Joof H M, Kwiatkowski D P, Mabey D C W, Bailey R L
Clinical Research Unit, Infectious Tropical Disease Department, London School of Hygiene and Tropical Medicine, London University, Keppel Street, London, UK.
Genes Immun. 2007 Jun;8(4):288-95. doi: 10.1038/sj.gene.6364384. Epub 2007 Mar 1.
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.
肿瘤坏死因子（TNF）被认为是沙眼衣原体（Ct）感染炎症和纤维化反应的关键介质。一项大型配对病例对照研究调查了主要组织相容性复合体（MHC）III类区域的推定功能性单核苷酸多态性（SNP），包括TNF及其紧邻的B细胞中κ轻链多肽基因增强子的核因子（IkappaBL）、类抑制剂1和淋巴毒素α（LTA），与眼部Ct感染瘢痕后遗症风险的关系。单倍型和连锁不平衡分析显示，在TNF - 308位置不同的两种单倍型会增加倒睫风险。TNF - 308A等位基因及其携带的单倍型与衣原体原体抗原刺激的淋巴细胞培养物中TNF产生增加相关。因此，TNF - 308A可能直接决定，或者是与衣原体感染后遗症风险增加相关的高TNF产生者表型的标志物。多变量分析为TNF基因座附近存在其他风险相关变异提供了证据。
