Department of Physiology, School of Medicine, University of Athens, Athens, Greece.
Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece.
J Autoimmun. 2014 Jun;51:89-98. doi: 10.1016/j.jaut.2013.04.005. Epub 2013 Jul 9.
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.
原发性干燥综合征（pSS）在 5-10%的患者中并发 B 细胞淋巴瘤。一些临床和血清学特征被提出作为这种并发症的不良预测因子，并定义了高风险 pSS 表型。我们旨在探讨先前描述的 B 细胞激活因子（BAFF）的多态性是否与 pSS 相关的淋巴瘤发生有关。在 111 例低危 pSS 患者（II 型）、82 例高危/淋巴瘤患者（I 型）和 137 例健康对照者（HC）中，通过 PCR 方法评估了 BAFF 基因的 5 个单核苷酸多态性（SNP）（rs1224141、rs12583006、rs9514828、rs1041569 和 rs9514827）。pSS 患者分为 II 型（无危险因素或无淋巴瘤发生）和 I 型（有危险因素或有淋巴瘤发生）。对所有变体在 pSS 组进行基因型和单倍型分析。由于 rs1041569 SNP 在 HC 组中不符合 Hardy-Weinberg 平衡（p<0.001），因此在与 HC 个体进行比较时，对所测试的五个 SNP 中的其余四个 SNP 进行了单倍型分析。高危 pSS 组与 HC 相比，BAFF 多态性 rs9514828 中的 T 等位基因频率较高。与低危 pSS 患者但与 HC 相比，高危 pSS 组 rs12583006 多态性的 AA 基因型和 TACAC 和 TACC 单倍型频率较低，TTTC 单倍型频率较高。低危 pSS 组与 HC 相比，rs12583006 变体的 T 等位基因和 AA 基因型频率较高。与 HC 相比，两个 pSS 组的 TATT 和 GTTC 单倍型频率增加，TTCT 单倍型频率降低。总之，这些发现表明宿主遗传背景在 pSS 相关淋巴瘤发生中的作用。pSS 相关 BAFF 基因单倍型的相互作用以及不同的 BAFF 遗传变异似乎促成了这种并发症。
