Tumour necrosis factor-α promoter polymorphisms in primary biliary cirrhosis
Tumour necrosis factor-α promoter polymorphisms in primary biliary cirrhosis
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DOI：
10.1016/s0168-8278(99)80067-1
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发表时间：
1999-02-01
影响因子：
25.7
通讯作者：
Bassendine, MF
中科院分区：
文献类型：
--
作者：
Jones, DEJ;Watt, FE;Bassendine, MF
背景/目标：患者近亲中原发性胆汁性肝硬化（PBC）的发病率增加，表明遗传因素在疾病易感性中发挥作用。据报道，PBC患者体外产生的肿瘤坏死因子（TNF）-α减少，表明这种细胞因子的潜在病因作用。本研究的目的是检测TNF-α基因启动子区的两个双等位基因多态性，这两个多态性可能在控制TNF-α分泌中发挥作用，作为PBC的候选易感基因座。通过聚合酶链反应分析了168例非亲缘PBC患者和145例本地非亲缘PBC患者TNF-α启动子区-238和-308位点的多态性，地理上匹配的正常个体。所有PBC受试者也进行了HLA DR 8基因分型，这是一个以前确定的易感位点在PBC.Results：-308 TNF 1/TNF 1基因型被认为是在PBC患者（66%）和对照组（60%）的相似比例。然而，该基因型在95例晚期PBC患者（组织学III/IV期）中的频率显著高于对照组（77%）（p
Background/aims: The incidence of primary biliary cirrhosis (PBC) is increased in the close relatives of patients, suggesting that genetic factors play a role in disease susceptibility. Decreased in vitro production of tumour necrosis factor (TNF)-alpha has been reported in PBC patients, suggesting a potential aetiological role for this cytokine. The aim of this study was to examine two biallelic polymorphisms in the promoter region of the TNF-alpha gene, which may play a role in the control of TNF-alpha secretion, as candidate susceptibility loci in PBC.Methods: The polymorphisms at positions -238 and -308 in the TNF-alpha promoter region were analysed by polymerase chain reaction in 168 unrelated PBC patients and 145 local unrelated, geographically matched normal individuals. All PBC subjects were also genotyped for HLA DR8, a previously identified susceptibility locus in PBC.Results: The -308 TNF1/TNF1 genotype was seen in a similar proportion of PBC patients (66%) and controls (60%). However, this genotype was found significantly more frequently in the 95 PBC patients with more advanced disease (histological stage III/IV) (77%) than in either controls (p