B-cell activating factor genetic variants in lymphomagenesis associated with primary Sjogren's syndrome
B-cell activating factor genetic variants in lymphomagenesis associated with primary Sjogren's syndrome
复制标题
DOI：
10.1016/j.jaut.2013.04.005
复制
发表时间：
2014-06-01
影响因子：
12.8
通讯作者：
Mavragani, Clio P.
中科院分区：
文献类型：
--
作者：
Nezos, Adrianos;Papageorgiou, Aristea;Mavragani, Clio P.
原发性干燥综合征(PSS)合并B细胞淋巴瘤的比例为5-10%。一些临床和血清学特征被认为是此类并发症的不利预测因素，并定义了高危PSS表型。我们的目的是探索先前描述的B细胞激活因子(BAFF)基因的多态性是否与PSS相关的淋巴肿大有关。采用聚合酶链式反应技术检测111例低危PSS患者(II型)、82例高危/淋巴瘤患者(I型)和137例健康对照(HC)的BAFF基因5个单核苷酸多态性(rs1224141、rs12583006、rs9514828、rs1041569和rs9514827)。将PSS患者分为I型和II型分别基于有无危险因素或发生淋巴瘤。对PSS组的所有变异体进行基因分型和单倍型分析。由于在HC组中rs1041569 SNP不符合Hardy-Weinberg平衡(p<；0.001)，所以在与HC个体进行比较时，在所测试的5个SNP中的其余4个进行了单倍型分析。高危PSS组rs9514828BAFF多态T等位基因频率明显高于HC组。与低危PSS组相比，高危PSS组rs12583006多态AA基因型频率低，TACAC和TACC单倍型频率低，TTTC单倍型频率高。与HC相比，低危PSS组rs12583006变异的小A等位基因和AA基因型的频率更高。与HC相比，两个PSS组的特征都是单倍型纹身和GTTC频率增加，TTCT频率降低。综上所述，这些发现表明宿主的遗传背景与PSS相关的淋巴肿大有关。与PSS相关的BAFF基因单倍型与不同的BAFF遗传变异的相互作用似乎是导致这种并发症的原因。(C)2013爱思唯尔有限公司。保留所有权利。
Primary Sjogren's syndrome (pSS) is complicated by B-cell lymphoma in 5-10% of patients. Several clinical and serological features are proposed as adverse predictors for such complication and define a high risk pSS phenotype. We aimed to explore whether previously described polymorphisms of the B-cell activating factor (BAFF) could be related to pSS-related lymphomagenesis. Five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) were evaluated in 111 low risk pSS patients (type II), 82 high risk/lymphoma patients (type I) and 137 healthy controls (HC) by PCR-based assays. The classification of pSS patients into types I and II was based on the presence or absence of risk factors or lymphoma development, respectively. Genotype and haplotype analysis was performed for all variants in the pSS groups. Since the rs1041569 SNP was not in Hardy-Weinberg equilibrium in the HC group (p < 0.001), haplotype analysis was performed in the remaining four out of the five SNPs tested when comparisons with HC individuals were performed. The high risk pSS group was characterized by higher frequency of the minor T allele of the rs9514828 BAFF polymorphism compared to HC. Compared to the low risk pSS patients but not the HC, the high risk pSS group exhibited lower frequencies of the AA genotype of the rs12583006 polymorphism as well as the TACAC and TACC haplotypes and higher frequency of the TTTC haplotype. The low risk pSS group exhibited higher frequency of the minor A allele and AA genotype of the rs12583006 Variant compared to HC. Both pSS groups were characterized by increased frequency of the haplotype TATT and GTTC and decreased frequency of the TTCT when compared to HC. Taken together, these findings suggest the implication of the host's genetic background in pSS-related lymphomagenesis. The interaction of pSS-related BAFF gene haplotypes together with distinct BAFF genetic variants appears to contribute to this complication. (C) 2013 Elsevier Ltd. All rights reserved.