Phosphodiesterase-5 gene (PDE5A) polymorphisms are associated with progression of childhood IgA nephropathy

The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). The present study was conducted to investigate the association among 16 single nucleotide polymorphisms (SNPs) of PDE5A and childhood IgAN. The genotyping data from 160 patients with childhood IgAN and 454 controls showed a significant difference in rs13124532 (codominant, P = 0.005; dominant, P = 0.005). Furthermore, patient subgroup analysis revealed an association between the development of proteinuria (>4 and ≤4 mg/m2/h) and rs13124532 (codominant, P = 0.008; dominant, P = 0.011), and between the nephrotic range proteinuria (> 40 mg/m2/h) and rs11734241 (dominant, P = 0.035), rs12510138 (dominant, P = 0.028), rs13134665 (dominant, P = 0.025), rs3822192 (dominant, P = 0.027), rs10013305 (dominant, P = 0.020), rs1480940 (dominant, P = 0.020), rs1480936 (dominant, P = 0.019), rs11947234 (dominant, P = 0.019), and rs2127823 (dominant, P = 0.026). The pathological findings showed that rs13124532 had an association with podocyte foot process effacement (codominant, P = 0.035; dominant, P = 0.044) and with pathological progression (codominant, P = 0.046). Our results suggest that PDE5A is associated with increased disease susceptibility, pathological progression, and development of proteinuria in childhood IgAN.