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 >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.
Hahn
Won-Ho
WH
Department of Pediatrics, East West Kidney Diseases Research Institute, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
Suh
Jin-Soon
JS
Cho
Seong Ho
SH
Cho
Byoung-Soo
BS
Kim
Sung-Do
SD
D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D003710:Demography; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics*; D050797:STAT4 Transcription Factor / Q000235:genetics*
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human