Coto-Segura Pablo, Gonzalez-Lara Leire, Gómez Juan, Eiris Noemí, Batalla Ana, Gómez Celia, Requena Sheila, Queiro Rubén, Alonso Belén, Iglesias Sara, Coto Eliecer
Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain; Dept Medicine, Universidad Oviedo, Oviedo, Spain.
Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
Hum Immunol. 2017 May-Jun;78(5-6):435-440. doi: 10.1016/j.humimm.2017.02.008. Epub 2017 Mar 1.
The IκBζ protein (NFKBIZ gene) is a nuclear inhibitor of NF-κB and plays an important role in the pathogenesis of Psoriasis (Psor). We sought to determine whether common NFKBIZ variants were associated with the risk of developing Psor. A total of 392 patients and 336 controls were genotyped for a common intron 10 indel that could affect pre-mRNA splicing. We found a significantly higher frequency of the insertion among the cw6-positive patients (p=0.01). Cw6-positive+intron 10 ins/ins were significantly more frequent in the patients (OR=3.61). The analysis of the cDNA from leukocytes showed a NFKBIZ transcript lacking exon 10, present in all the tested samples. This new alternative transcript lacks a domain predicted to interact with the NFKB1/p50 protein. Functional studies to define the effect of this alternative transcript on the regulation of the NF-κB pathway are necessary.
IκBζ蛋白（NFKBIZ基因）是一种核因子κB的核抑制剂，在银屑病（Psor）的发病机制中起重要作用。我们试图确定常见的NFKBIZ变异体是否与患Psor的风险相关。对总共392例患者和336例对照进行基因分型，检测一个可能影响前体mRNA剪接的常见内含子10插入缺失。我们发现cw6阳性患者中插入的频率显著更高（p = 0.01）。患者中cw6阳性+内含子10插入/插入的频率显著更高（比值比= 3.61）。对白细胞cDNA的分析显示，所有测试样本中均存在一种缺少外显子10的NFKBIZ转录本。这种新的可变转录本缺少一个预测与NFKB1/p50蛋白相互作用的结构域。有必要进行功能研究以确定这种可变转录本对核因子κB通路调控的影响。
