Bayley J-P, Ottenhoff T H M, Verweij C L
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Genes Immun. 2004 Aug;5(5):315-29. doi: 10.1038/sj.gene.6364055.
The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied -308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.
肿瘤坏死因子（TNF）启动子多态性（SNP）功能的体外研究受到众多关于该多态性与人类疾病关系的病例对照（关联）研究的推动，并且一些声称显示这些SNP具有功能作用的研究的出现，为对TNF在其感兴趣疾病中的作用感兴趣的研究人员提供了进一步的动力。在本综述中，我们考虑病例对照研究，重点关注自身免疫性和炎性疾病，如类风湿性关节炎、多发性硬化症、强直性脊柱炎和哮喘，以及包括疟疾、乙型和丙型肝炎感染、麻风病和败血症/脓毒性休克在内的传染病。我们还综述了关于各种TNF启动子多态性功能作用的现有证据。总体而言，病例对照研究结果不一，在大多数情况下，对于任何TNF多态性是否真的与疾病相关几乎没有共识，尽管在传染病尤其是疟疾方面结果更为一致。功能研究结果也参差不齐，但最近的研究表明，被大量研究的-308G/A多态性没有功能，而其他TNF多态性的功能仍存在争议。对TNF区域的研究越来越多地使用扩展单倍型，其能够更好地捕捉主要组织相容性复合体（MHC）区域的变异。
