Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
J Immunol Res. 2018 Dec 19;2018:6923213. doi: 10.1155/2018/6923213. eCollection 2018.
Tumor necrosis factor, alpha-induced protein 3 () gene encodes the A20 protein, an important negative feedback regulator of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) pathway. A coding variant, namely rs2230926, has been previously linked to B cell non-Hodgkin's lymphoma (NHL) development in patients with Sjogren's syndrome (SS) of French and UK origin. Herein, we aimed to determine the prevalence of rs2230926 in a Greek primary SS cohort and explore possible associations with disease characteristics. The rs2230926 gene variant was genotyped in 327 primary Greek SS patients (ninety-one complicated by NHL (SS-lymphoma)) and 448 Greek healthy controls (HC) of similar age and sex distribution. Clinical and laboratory characteristics were also recorded and gene expression of relevant genes of the NF-B pathway was quantitated by real-time PCR in available whole peripheral blood (PB) from 165 primary SS patients. Increased prevalence of the rs2230926 mutant variant was detected in both SS-lymphoma and SS-nonlymphoma subgroups compared to HC (8.8% vs. 7.6% vs. 3.6%, values: 0.04 and 0.03, respectively) in association with higher IgM, LDH serum levels, and PB transcripts but lower leucocyte and neutrophil counts. Of interest, approximately one-fifth of SS-lymphoma cases with age at disease onset ≤ 40 years carried the rs2230926 variant (18.2% vs. 3.6%, OR 95% (CI): 6.0 (1.8-19.8), value: 0.01). We postulate that deregulation of the NF-B pathway as a result of the rs2230926 aberration increases SS and SS lymphoma susceptibility particularly in patients with early disease onset.
肿瘤坏死因子-α诱导蛋白 3 () 基因编码 A20 蛋白，是核因子 kappa 轻链增强子活化 B 细胞（NF-B）通路的重要负反馈调节剂。一个编码变异体，即 rs2230926，先前与法国和英国来源的干燥综合征（SS）患者的 B 细胞非霍奇金淋巴瘤（NHL）发展有关。在此，我们旨在确定 rs2230926 在希腊原发性 SS 队列中的流行率，并探讨其与疾病特征的可能关联。对 327 例原发性希腊 SS 患者（91 例并发 NHL（SS-淋巴瘤））和 448 例年龄和性别分布相似的希腊健康对照者（HC）进行 rs2230926 基因变异体的基因分型。还记录了临床和实验室特征，并在 165 例原发性 SS 患者的可用全外周血（PB）中通过实时 PCR 定量测定 NF-B 通路的相关基因表达。与 HC 相比，在 SS-淋巴瘤和 SS-非淋巴瘤亚组中均检测到 rs2230926 突变变体的患病率增加（8.8%比 7.6%比 3.6%， 值：0.04 和 0.03），与更高的 IgM、LDH 血清水平和 PB 转录物相关，但白细胞和中性粒细胞计数较低。有趣的是，大约五分之一的发病年龄≤40 岁的 SS-淋巴瘤病例携带 rs2230926 变异体（18.2%比 3.6%，OR 95%（CI）：6.0（1.8-19.8）， 值：0.01）。我们假设 NF-B 通路的 rs2230926 异常失稳会增加 SS 和 SS 淋巴瘤的易感性，特别是在发病年龄较早的患者中。
