Clark Taane G, Diakite Mahamadou, Auburn Sarah, Campino Susana, Fry Andrew E, Green Angela, Richardson Anna, Small Kerrin, Teo Yik Y, Wilson Jonathan, Jallow Muminatou, Sisay-Joof Fatou, Pinder Margaret, Griffiths Michael J, Peshu Norbert, Williams Thomas N, Marsh Kevin, Molyneux Malcolm E, Taylor Terrie E, Rockett Kirk A, Kwiatkowski Dominic P
Wellcome Trust Centre for Human Genetics, University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
J Infect Dis. 2009 Feb 15;199(4):569-75. doi: 10.1086/596320.
The tumor necrosis factor gene (TNF) and lymphotoxin-alpha gene (LTA) have long attracted attention as candidate genes for susceptibility traits for malaria, and several of their polymorphisms have been found to be associated with severe malaria (SM) phenotypes. In a large study involving >10,000 individuals and encompassing 3 African populations, we found evidence to support the reported associations between the TNF -238 polymorphism and SM in The Gambia. However, no TNF/LTA polymorphisms were found to be associated with SM in cohorts in Kenya and Malawi. It has been suggested that the causal polymorphisms regulating the TNF and LTA responses may be located some distance from the genes. Therefore, more-detailed mapping of variants across TNF/LTA genes and their flanking regions in the Gambian and allied populations may need to be undertaken to find any causal polymorphisms.
肿瘤坏死因子基因(TNF)和淋巴毒素-α基因(LTA)长期以来一直作为疟疾易感性特征的候选基因受到关注,并且已发现它们的几种多态性与严重疟疾(SM)表型相关。在一项涉及超过10000人且涵盖3个非洲人群的大型研究中,我们发现有证据支持在冈比亚所报道的TNF -238多态性与严重疟疾之间的关联。然而,在肯尼亚和马拉维的队列中未发现TNF/LTA多态性与严重疟疾相关。有人提出,调节TNF和LTA反应的因果多态性可能位于距这些基因一定距离处。因此,可能需要对冈比亚及相关人群中TNF/LTA基因及其侧翼区域的变异进行更详细的定位,以找到任何因果多态性。