Ferguson Lynnette R, Huebner Claudia, Petermann Ivonne, Gearry Richard B, Barclay Murray L, Demmers Pieter, McCulloch Alan, Han Dug Yeo
Discipline of Nutrition, the University of Auckland, Auckland, New Zealand.
World J Gastroenterol. 2008 Aug 7;14(29):4652-61. doi: 10.3748/wjg.14.4652.
To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies.
DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-alpha receptor: -238 G-->A, -308 G-->A and -857C-->T, using a Taqman assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies.
Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, c2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, c2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, c2 = 4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, c2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, c2 = 4.86, P = 0.028).
TNF-alpha is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-alpha promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desirable for individuals with such affected genotypes.
在国际研究的背景下，调查肿瘤坏死因子-α（TNF-α）基因启动子中的单核苷酸多态性（SNP）在新西兰人群炎症性肠病（IBD）风险中所起的作用。
采用Taqman分析法，对来自新西兰坎特伯雷地区的388例克罗恩病（CD）患者、405例溃疡性结肠炎（UC）患者、27例未定型结肠炎（IC）患者以及201例随机选择的对照者的DNA样本，筛查TNF-α受体中的3种常见多态性：-238G→A、-308G→A和-857C→T。对这些多态性获得的数据以及其他已发表研究的数据进行荟萃分析。
携带-308G/A等位基因的个体患全结肠炎的风险显著增加（OR = 1.91，χ² = 17.36，P < 0.0001），在UC中需要进行肠切除的风险增加1.57倍（OR = 1.57，χ² = 4.34，P = 0.037）。携带-857C/T变异体可降低回结肠型CD的风险（OR = 0.56，χ² = 4.32，P = 0.037）以及肠切除的必要性（OR = 0.59，χ² = 4.85，P = 0.028）。诊断时为吸烟者的UC风险降低（OR = 0.48，χ² = 4.86，P = 0.028）。
TNF-α是一种已知在炎症反应中起作用的关键细胞因子，该基因座位于6号染色体p21的IBD3区域，已知与IBD风险增加相关。TNF-α启动子中的-308G/A SNP具有功能性，可能部分解释了与IBD3基因组区域相关的UC风险增加。-857C/T SNP可能降低某些群体的IBD风险。对于具有此类受影响基因型的个体，药物或营养基因组学方法可能是可取的。
