Linkage and association study of discoidin domain receptor 1 as a novel susceptibility gene for childhood IgA nephropathy

Abstract

Abstract.In several experimental studies, it has been suggested that discoidin domain receptor 1 (DDR1) plays an important role in the regulation of mesangial proliferation, glomerular basement membrane thickening, renal fibrosis, and in the development of inflammation in several tissue types, including renal tissues. The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the DDR1 gene and childhood IgA nephropathy (IgAN). The genotyping data of 180 childhood IgAN patients and 336 controls showed significant differences in the frequency of rs1264319 (dominant model, P=0.040). Subgroup analysis revealed that development of proteinuria (>4 and ≤4 mg/m 2 /h; n=131 and 49) was significantly associated with rs2267641 (codominant model, P=0.004; dominant, P=0.024; recessive, P=0.010) and rs9468844 (codominant model, P=0.003; dominant, P=0.017; recessive, P=0.012). Furthermore, rs1264319 frequencies were significantly different in those with pathologically mild and advanced disease subgroups (n=162 and 18; codominant and dominant model, P=0.022). Our results suggest that DDR1 gene is associated with increased susceptibility, pathological advancement, and the development of proteinuria in childhood IgAN.