Polymorphisms of signal transducers and activators of transcription 1 and 4 (STAT1 and STAT4) contribute to progression of childhood IgA nephropathy

Background: Several experimental studies have suggested that signal transducers and activators of transcription 1 and 4 (STAT1 and STAT4) play important roles in the regulation of mesangial proliferation and renal fibrosis, and in the development of inflammation in several types of glomerulonephritis. Methods: The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the STAT1 and STAT4 genes and childhood IgA nephropathy (IgAN). Results: Genotyping of 170 childhood IgAN patients and 442 controls showed no significant differences in allele frequency. However, patient subgroup analysis revealed that development of proteinuria (<= and >4 mg/m(2)/h) was associated with STAT1 rs10199181 (dominant model, P = 0.035) and high serum level of IgA with STAT1 rs6718902 (dominant model, P = 0.035) and STAT1 rs2280232 (codominant model, P = 0.014; dominant model, P = 0.022). Furthermore, some SNP frequencies were significantly different between patients with pathologically mild and advanced disease; STAT1 rs6718902 (overdominant model, P = 0.030), STAT1 rs10199181 (codominant model, P = 0.023; dominant model, P = 0.012: overdominant model, P = 0.018), and STAT4 rs7561832 (dominant model, P = 0.026; overdominant model, P = 0.029). Conclusions: Our results suggest that polymorphisms of STAT1 and STAT4 are associated with increased susceptibility, pathological advancement, and development of proteinuria in childhood IgAN. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.