Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Traditional Herb Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
Eur J Clin Invest. 2019 Mar;49(3):e13065. doi: 10.1111/eci.13065. Epub 2019 Jan 16.
Dysregulation of the type 1 interferon (IFN)-related signalling pathway predisposes one to autoimmune diseases. Possible associations of single-nucleotide polymorphisms (SNPs) of secreted phosphoprotein 1 (SPP1) and B lymphocyte kinase (BLK) of the type 1 IFN-related signalling pathway with autoimmune thyroid disease (AITD) in an ethnic Chinese (ie Taiwanese) population were tested.
Totally, 83 Hashimoto's thyroiditis (HT) patients, 319 Graves' disease (GD) patients and 369 controls were enrolled. Genotypes of the two SNPs (rs1126772 and rs1126616) of SPP1 and two SNPs (rs13277113 and rs2736340) of BLK were determined.
Our results showed reduced percentages of the G allele of rs13277113 of BLK in GD (P = 0.037, odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.62-0.99) and HT (P = 0.002, OR = 0.54, 95% CI = 0.36-0.81), compared to the controls. At the same time, lower frequencies of the C allele of rs2736340 of BLK in GD (P = 0.025, OR = 0.76, 95% CI = 0.60-0.97) and HT (P = 0.003, OR = 0.53, 95% CI = 0.35-0.81) than the controls were also observed. There were significantly higher AT haplotype frequencies of rs1327713 and rs2736340 in GD and HT patients than in the controls (P = 0.025, OR = 1.31, 95% CI = 1.03-1.67, and P = 0.003, OR = 1.89, 95% CI = 1.24-2.87, respectively). Moreover, the anti-microsomal antibody titre was associated with rs2736340.
Genetic variants of rs13277113 and rs2736340 of BLK were associated with susceptibility to GD, HT and AITD in an ethnic Chinese population. Our results suggest the BLK may participate in the pathogenesis of GD, HT and AITD.
1 型干扰素（IFN）相关信号通路的失调使个体易患自身免疫性疾病。检测了 1 型 IFN 相关信号通路中分泌磷蛋白 1（SPP1）和 B 淋巴细胞激酶（BLK）的单核苷酸多态性（SNP）与中国（即台湾）汉族人群自身免疫性甲状腺疾病（AITD）的可能关联。
共纳入 83 例桥本甲状腺炎（HT）患者、319 例格雷夫斯病（GD）患者和 369 例对照者。检测了 SPP1 的两个 SNP（rs1126772 和 rs1126616）和 BLK 的两个 SNP（rs13277113 和 rs2736340）的基因型。
我们的结果显示，BLK 的 rs13277113 的 G 等位基因在 GD（P=0.037，OR=0.78，95%CI=0.62-0.99）和 HT（P=0.002，OR=0.54，95%CI=0.36-0.81）患者中的百分比降低，与对照组相比。同时，BLK 的 rs2736340 的 C 等位基因在 GD（P=0.025，OR=0.76，95%CI=0.60-0.97）和 HT（P=0.003，OR=0.53，95%CI=0.35-0.81）患者中的频率也低于对照组。GD 和 HT 患者中 rs1327713 和 rs2736340 的 AT 单倍型频率明显高于对照组（P=0.025，OR=1.31，95%CI=1.03-1.67，和 P=0.003，OR=1.89，95%CI=1.24-2.87，分别）。此外，抗微粒体抗体滴度与 rs2736340 相关。
BLK 的 rs13277113 和 rs2736340 遗传变异与中国汉族人群 GD、HT 和 AITD 的易感性相关。我们的结果表明，BLK 可能参与了 GD、HT 和 AITD 的发病机制。
