Genetic contribution and associated pathophysiology in end-stage renal disease

Suraksha Agrawal¹, SS Agarwal¹, Sita Naik<sup>2

1</sup>Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India; ²Department of Clinical Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

Abstract: End-stage renal disease (ESRD) or chronic kidney disease (CKD) is the terminal state of the kidney when its function has been permanently and irreversibly damaged. A wide variety of etiologies and pathological processes culminate in ESRD, and both environmental and genetic factors contribute to its development and progression. Various reports suggest that susceptibility to develop ESRD has a significant genetic component. These studies include familial aggregation studies, comparisons of incidence rates between different racial or ethnic populations, and segregation analysis. Genetic approaches have been used to identify genes that contribute to genetic susceptibility. Many studies have now been carried out assessing the contribution of specific “candidate genes”, which correlate with different functions that are involved in the renal pathogenesis. Independent studies for specific associated genes have frequently provided contradictory results. This may be due, in part, to the modest contribution to genetic susceptibility which these genes impart. With the availability of different genome-wide association studies, chromosomal regions harboring novel, previously unrecognized, genes that may contribute to renal diseases have been recently reported. We have focused on different genetic studies conducted on ESRD and have discussed the strength and weaknesses of these studies. The nonmuscle myosin heavy chain 9 gene (MYH9) and renin–angiotensin system (RAS) have been discussed in detail.

Keywords: genetic polymorphism MYH9, renin–angiotensin system (RAS), genome-wide analysis (WGA or GWA), end-stage renal disease