The Susceptibility Genes in Diabetic Nephropathy

Background: Diabetes mellitus (DM) poses a severe threat to global public health. Diabetic nephropathy (DN) is one of the most common complications of diabetes and the leading cause of end-stage renal disease (ESRD). Approximately 30-40% of DM patients in the world progress to ESRD, which emphasizes the effect of genetic factors on DN. Family clustering also supports the important role of hereditary factors in DN and ESRD. Therefore, a large number of genetic studies have been carried out to identify susceptibility genes in different diabetic cohorts. Extensive susceptibility genes of DN and ESRD have not been identified until recently. Summary and Key Messages: Some of these associated genes function as pivotal regulators in the pathogenesis of DN, such as those related to glycometabolism and lipid metabolism. However, the functions of most of these genes remain unclear. In this article, we review several susceptibility genes according to their genetic functions to make it easier to determine their exact effect on DN and to provide a better understanding of the advancements from genetic studies. However, several challenges associated with investigating the genetic factors of DN still exist. For instance, it is difficult to determine whether these variants affect the expression of the protein they encode or other cytokines. More efforts should be made to determine how these genes influence the progression of DN. In addition, many results could not be replicated among races, suggesting that the association between genetic polymorphisms and DN is race-specific. Therefore, large, well-designed studies involving more relevant variables and ethnic groups and more relevant functional studies are urgently needed. These studies may be beneficial and retard the progression of DN by early intervention, especially for patients who carry certain risk alleles or genotypes.