Angiotensin II receptor type 1 A1166C modifies the association between angiotensinogen M235T and chronic kidney disease

Single nucleotide polymorphisms (SNPs) in renin-angiotensin system (RAS) genes are associated with RAS imbalance and chronic kidney disease (CKD). We performed a case-control study and meta-analysis to investigate the association between angiotensinogen (AGT) M235T polymorphism and CKD. A total of 634 patients with end-stage renal disease and 739 healthy controls were studied. We also searched PubMed and the Cochrane Library to identify prospective observational studies published before December 2015. We found that the TT and MT genotypes were associated with a higher risk of CKD than the MM genotype (odds ratio [OR]: 3.56; 95% confidence interval [CI]: 1.14-11.16 and OR: 2.93; 95% CI: 0.91-9.46, respectively). Thirty-eight study populations were included in the meta-analysis. The T allele was associated with a higher risk of CKD than the M allele in all populations (OR: 1.19; 95% CI: 1.08-1.32). The OR was 1.33 in Asians (95% CI: 1.06-1.67) and 1.10 in Caucasians (95% CI: 1.02-1.18). Evaluation of gene-gene and gene-environment interactions using epistasis analysis revealed an interaction between AGT M235T and angiotensin II receptor type 1 A1166C in CKD (OR: 0.767; 95% CI: 0.609-0.965). Genetic testing for CKD in high-risk individuals may be an effective strategy for CKD prevention.