Type 2 diabetes nephropathy is a multifactorial trait whose threshold or limit for the phenotypic expression depends on the additive effect of multiple loci and environmental factors that are specific to each population. After the sequencing of human genome more susceptibility loci through linkage studies and association have been found. The association studies showed involvement 69 loci, whereas genetic linkage studies involved 24 loci. Among environmental factors, genetically unknown foods and excessive consumption of beverages with sweeteners has been reported. However, despite wide evidence in the genetic component in the development of kidney damage, the environment participation is not evident in several perinatal studies. One of the approaches proposed given the genetic heterogeneity that influences nephropathy, are epistasis studies, which will become increasingly important in the upcoming years.