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

ABSTRACT

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 >4mg/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.