The association between rs1893217, rs478582 in PTPN2 and T1D risk with different diagnosed age, and related clinical characteristics in Chinese Han population
The association between rs1893217, rs478582 in PTPN2 and T1D risk with different diagnosed age, and related clinical characteristics in Chinese Han population
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中国汉族人群PTPN2中rs1893217、rs478582与T1D风险与不同诊断年龄及相关临床特征的关系
DOI：
10.1080/08916934.2019.1608191
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发表时间：
2019-02-17
期刊：
影响因子：
3.5
通讯作者：
Xu, Kuanfeng
中科院分区：
文献类型：
--
作者：
Chen, Shu;Fan, Hongqi;Xu, Kuanfeng
目的：在中国汉族人群中研究蛋白酪氨酸磷酸酶非受体型2（PTPN2）基因多态性（rs1893217和rs478582）与不同诊断年龄的1型糖尿病（T1D）风险以及相关临床特征之间的关联。
方法：对2270名中国汉族个体（1023例T1D患者和1247名健康对照）进行rs1893217和rs478582基因分型。对306例新诊断的T1D患者基于标准混合餐耐量试验测定C肽水平。此外，通过多色流式细胞术对40名健康对照分析不同的T细胞亚群。
结果：在加性模型下，rs1893217和rs478582均未显示与T1D风险有任何关联。对T1D诊断年龄进行分层分析显示，rs1893217（而非rs478582）与诊断年龄≤18岁的T1D患者显著相关，而与诊断年龄＞18岁的患者均无关联。我们还发现rs1893217的锌转运体8自身抗体（ZnT8A）阳性率较高（CC与TT携带者相比，比值比（OR）=2.07，95%置信区间（CI）：1.07 - 4.03，p = 0.026）以及蛋白酪氨酸磷酸酶样蛋白抗体（IA - 2A）阳性率较高（CT与TT携带者相比，OR = 1.36，95%CI：1.02 - 1.80，p = 0.038）。此外，对于rs478582，与TT相比，携带CC/CT的健康个体的初始调节性T细胞（Treg）亚群的频率和Helios表达显著降低（分别为p = 0.049和0.048），但分泌型或活化型Treg亚群无此情况。另外，我们未发现这两种多态性与新诊断的T1D患者的残余β细胞功能之间有任何关联。
结论：我们的结果表明rs1893217可能增加早发型T1D的风险并影响体液免疫，而rs478582可能影响Treg亚群。
Abstract Objective: To investigate the association between polymorphisms in PTPN2 (rs1893217 and rs478582) and type 1 diabetes (T1D) risk with different diagnosed age, as well as related clinical characteristics in Chinese Han population. Methods: A total of 2270 Chinese Han individuals (1023 T1D patients and 1247 healthy controls) were genotyped for rs1893217 and rs478582. And 306 newly diagnosed T1D patients were measured for C-peptide levels based on a standard mixed-meal tolerance test. In addition, 40 healthy controls were analyzed for different T cell subsets by multi-color flow cytometry. Results: Neither rs1893217 nor rs478582 showed any association with T1D risk under an additive model. Stratified analysis for T1D diagnosed age revealed that rs1893217, but not rs478582, was significantly associated with T1D patients diagnosed age ≤18 (OR =0.80, 95% CI: 0.67–0.97, p = 0.02). For those diagnosed age >18, neither of them showed any association. We also found that rs1893217 had a higher positive rate of ZnT8A (CC vs. TT carrier, OR = 2.07, 95% CI: 1.07–4.03, p = 0.026) and IA-2A (CT vs. TT carrier, OR = 1.36, 95% CI: 1.02–1.80, p = 0.038). Furthermore, for rs478582, compared with TT, healthy individuals carrying CC/CT carriers had significantly lower frequency and Helios expression of naive Treg subsets (p = 0.049 and 0.048 respectively), but not secreting or activating Treg subsets. In addition, we did not find any association between these two polymorphisms and residual β-cell function in newly diagnosed T1D patients. Conclusions: Our results suggest that rs1893217 may increase the risk of early-onset T1D and affect humoral immunity, while rs478582 may affect Treg subsets.