Polymorphisms of CXCL8 and its receptor CXCR2 contribute to the development and progression of childhood IgA nephropathy

Many studies have suggested that CXCL8 and CXCR2 play an important role in the pathogenesis of several types of renal diseases. However, there is no prior study on the association between polymorphisms of these genes and IgA nephropathy (IgAN), especially in children. The genotyping data from 192 patients with childhood IgAN and 397 controls showed significant differences in the frequencies of the CXCL8 gene with rs2227306 (dominant, P = 0.019; overdominant, P = 0.009), rs2227543 (dominant, P = 0.01; overdominant, P = 0.0057), and rs4073 (codominant, P = 0.034; dominant, P = 0.011; overdominant, P = 0.022). In addition, 2 single-nucleotide polymorphism frequencies of the CXCR2 gene (rs4674257 and rs4674259) significantly differed between the patients with pathologically mild and patients with advanced disease. Further, 5 single-nucleotide polymorphisms of the CXCL8 and CXCR2 genes significantly differed in the patients with infiltration of inflammatory cells on the renal biopsy samples. The results of this study suggest that polymorphisms of CXCL8 are associated with increased susceptibility to IgAN, and polymorphisms of CXCR2 with the pathological progression of childhood IgAN. These genetic variations might provide insight into novel individualized antichemokine regimens for treatment.