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.
Keywords: PTPN2; polymorphism; type 1 diabetes.