Evaluation of the role of B7-H3 haplotype in association with impaired B7-H3 expression and protection against type 1 diabetes in Chinese Han population
Evaluation of the role of B7-H3 haplotype in association with impaired B7-H3 expression and protection against type 1 diabetes in Chinese Han population
复制标题
中国汉族人群中 B7-H3 单倍型与 B7-H3 表达受损及预防 1 型糖尿病相关的作用评估
DOI：
10.1186/s12902-020-00592-7
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发表时间：
2020
影响因子：
2.7
通讯作者：
Zhang Xueguang
中科院分区：
文献类型：
--
作者：
Ding Sisi;Shan Yimei;Sun Lili;Li Sicheng;Jiang Rong;Chang Xin;Huang Ziyi;Sun Jing;Liu Cuiping;Fang Chen;Zhang Xueguang
研究背景1型糖尿病（T1 D）是一种T细胞介导的自身免疫性疾病，由胰岛素分泌细胞的破坏引起。B7-H3（CD 276）在T细胞应答中起着至关重要的作用。然而，B7-H3在T1 D中的表达及其临床意义尚不清楚。本研究旨在探讨B7-H3表达与T1 D患者临床参数之间的相关性。方法采用聚合酶链反应（PCR）直接测序法对121例T1 D患者和120例健康对照者的B7-H3基因4个单核苷酸多态性（SNPs）进行基因分型。流式细胞术检测外周血淋巴细胞膜B7-H3（mB 7-H3）的表达。结果T1 D患者血清中可溶性B7-H3（sB 7-H3）水平明显低于对照组（OR：0.31，95%CI：0.16-0.61）。T1 D患者外周血单核细胞B7-H3表达显著上调，且与ALT、120 min快速C肽、HbAlc、IFN-γ、IL-6、TNF-α等临床指标呈正相关（P< 0.05）。T1 D患者血清sB 7-H3水平升高（P< 0.0001）。B7-H3-T-A-C-T与sB 7-H3释放减少有关，但与膜型sB 7-H3释放无关。结论B7-H3可能是T1 D发病的潜在生物标志物。B7-H3-T-A-C-T多态性变异与T1 D的低风险以及sB 7-H3的释放较少相关。
BackgroundType 1 Diabetes (T1D) is a T cell-mediated autoimmune disorder caused by the destruction of insulin-secreting cells. B7-H3 (CD276) plays a vital role in T cell response. However, B7-H3 expression and its clinical significance in T1D remain unclear. The aim of this study was to investigate the correlations between the expression of B7-H3 and clinical parameters in T1D patients. The possible role of B7-H3 gene variants with T1D was also discussed.MethodsFour B7-H3 single nucleotide polymorphisms (SNPs) were genotyped in 121 T1D patients and 120 healthy controls by polymerase chain reaction (PCR) direct sequencing. Expression of membrane B7-H3 (mB7-H3) in peripheral blood lymphocytes was determined by flow cytometry. Levels of soluble B7-H3 (sB7-H3) in serum were analyzed by enzyme linked immunosorbent assay (ELISA).ResultsThe B7-H3 haplotype T-A-C-T was less frequently observed in T1D patients compared to the controls (OR: 0.31, 95% CI: 0.16–0.61). B7-H3 expression on monocytes showed significant upregulation in T1D patients and was positively correlated with several clinical features including ALT, fast C-peptide 120 min, HbAlc, IFN-γ, IL-6 and TNF-α (P< 0.05). The concentration of sB7-H3 in serum increased in T1D patients(P< 0.0001). We also observed that B7-H3-T-A-C-T was associated with the decreased release of sB7-H3 but not the membrane form.ConclusionsB7-H3 may act as a potential biomarker related to the pathogenesis of T1D. The B7-H3-T-A-C-T polymorphism variant is associated with the low risk of T1D as well as less release of sB7-H3.