Associations of secreted phosphoprotein 1 and B lymphocyte kinase gene polymorphisms with autoimmune thyroid disease

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Association between chronic periodontitis and the risk of Alzheimer’s disease: combination of text mining and GEO dataset

“…Secreted phosphoprotein 1 (SPP1) is a secreted glycophosphate protein with a wide range of functions and is also known as osteopontin, which plays an indispensable role in B cell-triggered cellular immunity [39,40]. At the same time, it plays a significant role in numerous autoimmune diseases, e.g., rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis [41]. Studies have shown that SPP1 levels in pyramidal neurons in the hippocampus of AD patients are significantly elevated [42].…”

BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder

“…Moreover, previous studies indicated that BLK was linked to numerous autoimmune diseases, 15‐19 the relationship of BLK polymorphism with NMOSD predisposition has not been reported. To the best of our knowledge, this study is the first to explore the effect of genetic polymorphisms in BLK variants on NMOSD occurrence among the Chinese Han population.…”

“… 13 , 14 Furthermore, BLK is involved in the immune tolerance of B lymphocytes, affecting the function of B cells, which may lead to autoreactive or regulatory cellular responses, increasing the risk of autoimmune diseases. Most studies have provided reliable evidence that the single nucleotide polymorphisms (SNPs) of BLK exert a key role in susceptibility to various autoimmune disorders, such as SLE, 15 rheumatoid arthritis (RA), 16 SS, 17 thyroid disorders, 18 and systemic sclerosis. 19 Similarly, NMOSD is also mainly a B cell‐mediated autoimmune disease.…”

Integrative analysis of key candidate genes and signaling pathways in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy by bioinformatics

“…SPP1, also named osteopontin, plays an important role in cell-mediated immunity and immunoglobulin production by B cells [ 39 , 40 ]. It is involved in various autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis [ 41 ]. It was demonstrated that SPP1 levels were increased in the serum of patients suffering from Graves’ disease [ 42 ].…”