Campbell Sarah J, Sabeti Pardis, Fielding Katherine, Sillah Jackson, Bah Boubacar, Gustafson Per, Manneh Kebba, Lisse Ida, Sirugo Giorgio, Bellamy Richard, Bennett Steve, Aaby Peter, McAdam Keith P W J, Bah-Sow Oumou, Lienhardt Christian, Hill Adrian V S
The Henry Wellcome Building of Genomic Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
Immunogenetics. 2003 Oct;55(7):502-7. doi: 10.1007/s00251-003-0602-9. Epub 2003 Aug 29.
Evidence for linkage between tuberculosis and human chromosomal region Xq26 has previously been described. The costimulatory molecule CD40 ligand, encoded by TNFSF5 and located at Xq26.3, is a promising positional candidate. Interactions between CD40 ligand and CD40 are involved in the development of humoral- and cell-mediated immunity, as well as the activation of macrophages, which are the primary host and effector cells for Mycobacterium tuberculosis. We hypothesised that common variation within TNFSF5 might affect susceptibility to tuberculosis disease and, thus, might be responsible for the observed linkage to Xq26. Sequencing 32 chromosomes from a Gambian population identified nine common polymorphisms within the coding, 3' and 5' regulatory sequences of the gene. Six single nucleotide polymorphisms (SNPs) and a 3' microsatellite were genotyped in 121 tuberculosis patients and their available parents. No association with tuberculosis was detected for these variants using a transmission disequilibrium test, although one SNP at -726 showed some evidence of association in males. This finding, however, did not replicate in a separate case control study of over 1,200 West African individuals. We conclude that common genetic variation in TNFSF5 is not likely to affect tuberculosis susceptibility in West Africa and the linkage observed in this region is not due to variation in TNFSF5.
此前已有关于结核病与人类染色体Xq26区域之间连锁关系的证据描述。由TNFSF5编码且位于Xq26.3的共刺激分子CD40配体是一个很有前景的定位候选基因。CD40配体与CD40之间的相互作用参与体液免疫和细胞介导免疫的发展，以及巨噬细胞的激活，而巨噬细胞是结核分枝杆菌的主要宿主和效应细胞。我们推测TNFSF5内的常见变异可能会影响结核病易感性，因此可能是观察到的与Xq26连锁的原因。对来自冈比亚人群的32条染色体进行测序，在该基因的编码区、3'和5'调控序列中鉴定出9个常见多态性。在121例结核病患者及其可获得的父母中对6个单核苷酸多态性（SNP）和一个3'微卫星进行了基因分型。使用传递不平衡检验未检测到这些变异与结核病的关联，尽管-726处的一个SNP在男性中显示出一些关联证据。然而，这一发现并未在一项超过1200名西非个体的独立病例对照研究中得到重复验证。我们得出结论，TNFSF5中的常见遗传变异不太可能影响西非的结核病易感性，且在该区域观察到的连锁并非由于TNFSF5的变异所致。
