A(-20)C polymorphism of the angiotensinogen gene and progression of IgA nephropathy

Background. The M235T polymorphism of the angiotensinogen gene (AGT) is associated with an increased risk of primary hypertension, which may then lead to progressive renal disease. Recent studies showed that nucleotide substitution in the 5' upstream core promoter region of A G T affects the basal transcription rate of the gene. Methods. To evaluate the role of AGT polymorphisms in the progression of IgA nephropathy (IgAN), we analyzed the association of A(-20)C and M235T polymorphisms with renal prognosis in histologically-proven IgAN patients using the Kaplan-Meier method and Cox proportional hazards regression model. Results. The incidence of hypertension during the course was associated with T235, but not with C(-20). The renal survival rate for 137 patients with creatinine clearance (Cc,) of 70 mL/min or greater at the time of renal biopsy, and follow-up time of two years or more was significantly lower in the patients with C(-20) (P = 0.008). The Cox proportional hazards regression model showed an increased hazard ratio (HR) for urinary protein (more than 2 g/day) of 28.3 (95% CI, 7.3 to 109.8; P < 0.001), hypertension at the time of renal biopsy of 4.6 (95% CI, 1.8 to 11.9; P = 0.002), and C(-20) of 3.6 (95% CI, 1.5 to 8.7; P = 0.004). Conclusion. This work provides evidence that the C(-20) polymorphism of AGT, a subset of T235 alleles, is associated with progression of renal dysfunction in IgAN.