PTPN22 and TYK2 genes polymorphisms contribute to neuropsychiatric systemic lupus erythematosus (NPSLE) in Chinese Han

Background: Neuropsychiatric manifestations pose diagnostic and therapeutic challenges in systemic lupus erythematosus (SLE). The aim of this study was to investigate whether the PTPN22, IRF5 and TYK2 polymorphisms are involved in the development of NPSLE. Material and methods: The association was investigated between three immune-associated genes (PTPN22, IRF5 and TYK2) polymorphisms and SLE patients with/without NP symptoms in Chinese Han population. And the relationship between clinical manifestations of neuropsychiatic SLE and SNPs were also assessed. Results: The allele distributions of TYK2 rs280500 and PTPN22 rs1217418 in the NPSLE group was significantly lower than that in the non-NPSLE group (rs280500: OR = 0.44, 95% CI = 0.27-0.74, P = 0.001, Padj = 0.005; rs1217418: OR = 0.41, 95% CI = 0.23-0.74, P = 0.002, Padj = 0.014). Significant association were detected between the allele distributions of TYK2 rs280500 and PTPN22 rs1217418 and SLE (NPSLE and non-NPSLE) compared with the controls (rs280500: OR = 0.62, 95% CI = 0.47-0.83, P = 0.0009, Padj = 0.0045; rs1217418: OR = 0.63, 95% CI = 0.47-0.84, P = 0.001, Padj = 0.007). HapGAGGT in TYK2 might confer protective effect on NPSLE compared to non-NPSLE group (OR = 0.43, 95% CI = 0.09-1.99, P = 0.006, Padj = 0.042). Moreover, no correlation between any clinical manifestations (Polyneuropathy, Cognitive disorders, Seizures, Anxiety disorders, Psychosis, Autonomic disorder, headache) and the allele frequencies for PTPN22, TYK2 and IRF5 polymorphisms was detected. Conclusions: Our findings implied that the genetic polymorphisms (rs280500 in TYK2 and rs1217418 in PTPN22) might be protective factors in the development of NPSLE in Chinese Han.