The Role of Renin Angiotensin Aldosterone System Genes in Diabetic Nephropathy

The role of the renin angiotensin aldosterone system (RAAS) and the gene variants of its components in susceptibility to diabetic nephropathy (DN) have been investigated in numerous studies. The effects of some RAAS gene variants, including angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R), on the risk for DN have been studied more extensively, but there has been controversy. The reasons for controversy in this field could be attributed to the effect of ethnicity, gender, stage of diabetes complications, the presence of intrarenal RAAS, methodologic limitations of the association studies in multifactorial diseases, inadequate sample size, genetic heterogeneity, and the lack of studies that involved all RAAS genes and their interactions. This review looks at the current available information about the role of all RAAS gene variants in the pathogenesis of DN. Further, the concomitant study of both systemic and local RAAS, counter-regulators of ACE and ACE2, and also AT1R and angiotensin II type 2 receptor (AT2R) genes could help to elucidate the role of the genes of this system in the pathogenesis of DN.