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英国和荷兰结节病中抑制蛋白κBα(IkappaBα)启动子多态性

Inhibitor kappa B-alpha (IkappaB-alpha) promoter polymorphisms in UK and Dutch sarcoidosis.

作者信息

Abdallah A, Sato H, Grutters J C, Veeraraghavan S, Lympany P A, Ruven H J T, van den Bosch J M M, Wells A U, du Bois R M, Welsh K I

机构信息

Clinical Genomics Group, Royal Brompton Hospital, Imperial College, London, UK.

出版信息

Genes Immun. 2003 Sep;4(6):450-4. doi: 10.1038/sj.gene.6364001.

Abstract

The aetiology of sarcoidosis is uncertain; current thinking implicates exposure of genetically susceptible hosts to environmental factors. The nuclear factor kappa B (NF-kappaB) family of transcription factors are critical regulators of immediate transcriptional responses in inflammatory situations and immune responses. Inhibitor kappa B-alpha (IkappaB-alpha) inhibits NF-kappaB and plays a major role in controlling its activity. We investigated IkappaB-alpha promoter polymorphisms using sequence-specific primer-polymerase chain reaction, at positions -881 (A/G), -826 (C/T), and -297 (C/T) in Caucasian sarcoidosis patients (UK and Dutch [NL]), each with their own controls. Disease severity at presentation was assigned using chest radiography and pulmonary function indices. In the combined populations, the -297T allele carriage was more prevalent in patients than in controls (P=0.008). Three common haplotypes were found, of which haplotype 2 (GTT) was significantly associated with sarcoidosis in comparison with control subjects (P=0.01). Subgroup analysis revealed that the -826T allelic carriage was most prevalent in stage II disease, and more prevalent in stage III than in stage IV (P=0.01). The -826T allelic carriage did not show any association with lung function. These results indicate that the NF-kappaB activation pathway might be associated with the inflammation of sarcoidosis.

摘要

结节病的病因尚不确定;目前的观点认为,遗传易感性宿主暴露于环境因素会引发该病。转录因子核因子κB(NF-κB)家族是炎症反应和免疫反应中即时转录反应的关键调节因子。抑制因子κB-α(IkappaB-α)抑制NF-κB,并在控制其活性方面发挥主要作用。我们使用序列特异性引物聚合酶链反应,对英国和荷兰白种人结节病患者及其各自的对照组,在-881(A/G)、-826(C/T)和-297(C/T)位点研究了IkappaB-α启动子多态性。通过胸部X线摄影和肺功能指标确定就诊时的疾病严重程度。在合并人群中,-297T等位基因携带者在患者中比在对照组中更常见(P=0.008)。发现了三种常见单倍型,其中单倍型2(GTT)与对照组相比,与结节病显著相关(P=0.01)。亚组分析显示,-826T等位基因携带者在Ⅱ期疾病中最为常见,在Ⅲ期比在Ⅳ期更常见(P=0.01)。-826T等位基因携带者与肺功能无任何关联。这些结果表明,NF-κB激活途径可能与结节病的炎症有关。

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