Allen R D
Department of Biology, Indiana University-Purdue University at Indianapolis, 46202, USA.
Mol Immunol. 1999 Oct-Nov;36(15-16):1017-27. doi: 10.1016/s0161-5890(99)00127-3.
As more and more polymorphisms are discovered in the genes encoding cytokines, a crucial question is whether this polymorphism has any functional effect. One of the most widely studied cytokine genes in this respect is the gene encoding human TNF-alpha. Much of the literature investigating the issue of whether TNF-alpha promoter polymorphisms have any functional effect on TNF-alpha transcription or influence disease susceptibility appears to report negative results, giving the appearance and leading some authors to conclude that polymorphism at this locus is functionally silent and exists only because of linkage disequilibrium with selectable HLA alleles. This review presents a new analysis of the available data which suggests that polymorphism in the TNF-alpha promoter is not randomly distributed and therefore that it most likely does have some functional and selectable effect. Further, a comparison of available data suggests that there is more consensus in the literature than may at first appear to be the case.
随着越来越多编码细胞因子的基因中的多态性被发现，一个关键问题是这种多态性是否具有任何功能效应。在这方面研究最广泛的细胞因子基因之一是编码人类肿瘤坏死因子-α（TNF-α）的基因。许多研究TNF-α启动子多态性是否对TNF-α转录有任何功能效应或影响疾病易感性问题的文献似乎都报告了阴性结果，给人的印象是，一些作者据此得出结论，该位点的多态性在功能上是沉默的，其存在仅仅是由于与可选择的人类白细胞抗原（HLA）等位基因的连锁不平衡。本综述对现有数据进行了新的分析，结果表明TNF-α启动子中的多态性并非随机分布，因此很可能确实具有某种功能和选择效应。此外，对现有数据的比较表明，文献中的共识比最初看起来的要多。
