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B-lymphocyte-activating factor is a potential biomarker associated with susceptibility to Graves’ disease in Iraqi women
Egyptian Journal of Medical Human Genetics Pub Date : 2023-11-17 , DOI: 10.1186/s43042-023-00455-5
Hiba Y. Ibrahim , Ghassan M. Sulaiman , Ali H. Ad’hiah , Mohamed S. Al-shammaa

B-lymphocyte-activating factor (BAFF) is a cytokine involved in regulating the development and maturation of B lymphocyte and has been shown to be up-regulated in patients with Graves’ disease (GD). However, the association of TNFSF13B variants (the gene that encodes BAFF) with the risk of GD has not been well explored. In this case–control study, the aim was to evaluate the role of BAFF, in terms of serum level and polymorphism, in the etio-pathogenesis of GD. Therefore, serum BAFF concentrations were analyzed in Iraqi women with GD and age-matched control women (n = 90 and 93, respectively) using an ELISA kit. In addition, two promoter variants of the TNFSF13B gene, rs9514827 (T > C) and rs9514828 (C > T), were genotyped using a PCR–RFLP-based assay. Median BAFF concentrations (interquartile range) were significantly elevated in GD patients compared to controls (1525 [1327–1840] vs. 689 [585–807] pg/mL; probability [p] < 0.001). Elevated BAFF concentrations were a reliable predictor of GD as indicated by the area under the curve of 0.971. BAFF was positively correlated with triiodothyronine (correlation coefficient [rs] = 0.216; p = 0.041) and thyroxine (rs = 0.269; p = 0.01) in GD patients. Mutant alleles, rs9514827 C (odds ratio [OR] = 2.00; p = 0.008; corrected p [pc] = 0.048) and rs9514828 T (OR = 2.15; p = 0.002; pc = 0.012), as well as genotypes, rs9514827 CC (OR = 4.29; p = 0.032; pc = 0.192) and rs9514828 TT (OR = 4.57; p = 0.003; pc = 0.018), were associated with a greater risk of GD. Besides, the C-T haplotype (rs9514827-rs9514828) was also linked to an elevated risk of GD among Iraqi women (OR = 2.71; p = 0.006; pc = 0.024). BAFF showed up-regulated levels in the serum of women with GD. In light of this, BAFF has been proposed as a reliable prognostic biomarker for GD. Regarding its relationship to thyroid hormones, BAFF showed a positive correlation with triiodothyronine and thyroxine. Both variants (rs9514827 and rs9514828) of the TNFSF13B gene showed an association with susceptibility to GD, and rs9514828 may have up-regulatory effects on BAFF levels.

中文翻译:

B 淋巴细胞激活因子是与伊拉克妇女格雷夫斯病易感性相关的潜在生物标志物

B 淋巴细胞激活因子 (BAFF) 是一种参与调节 B 淋巴细胞发育和成熟的细胞因子,已被证明在格雷夫斯病 (GD) 患者中表达上调。然而,TNFSF13B 变体(编码 BAFF 的基因)与 GD 风险之间的关系尚未得到充分探索。在这项病例对照研究中,目的是评估 BAFF 在 GD 发病机制中的血清水平和多态性的作用。因此,使用 ELISA 试剂盒对伊拉克 GD 妇女和年龄匹配的对照妇女(分别为 n = 90 和 93)的血清 BAFF 浓度进行了分析。此外,使用基于 PCR-RFLP 的测定法对 TNFSF13B 基因的两个启动子变体 rs9514827 (T > C) 和 rs9514828 (C > T) 进行了基因分型。与对照组相比,GD 患者的中位 BAFF 浓度(四分位距)显着升高(1525 [1327–1840] vs. 689 [585–807] pg/mL;概率 [p] < 0.001)。BAFF 浓度升高是 GD 的可靠预测因子,如曲线下面积 0.971 所示。在 GD 患者中,BAFF 与三碘甲状腺原氨酸(相关系数 [rs] = 0.216;p = 0.041)和甲状腺素(rs = 0.269;p = 0.01)呈正相关。突变等位基因,rs9514827 C(比值比 [OR] = 2.00;p = 0.008;校正 p [pc] = 0.048)和 rs9514828 T(OR = 2.15;p = 0.002;pc = 0.012),以及基因型,rs9514827 CC (OR = 4.29;p = 0.032;pc = 0.192)和 rs9514828 TT(OR = 4.57;p = 0.003;pc = 0.018)与较高的 GD 风险相关。此外,CT单倍型(rs9514827-rs9514828)也与伊拉克女性GD风险升高相关(OR = 2.71;p = 0.006;pc = 0.024)。患有 GD 的女性血清中 BAFF 水平升高。鉴于此,BAFF 被提议作为 GD 的可靠预后生物标志物。关于与甲状腺激素的关系,BAFF与三碘甲状腺原氨酸和甲状腺素呈正相关。TNFSF13B 基因的两个变体(rs9514827 和 rs9514828)均显示与 GD 易感性相关,并且 rs9514828 可能对 BAFF 水平具有上调作用。
更新日期:2023-11-17
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