Three new genetic risk factors for kidney disease in type 2 diabetes

Three genetic variables are identified as predictors of chronic kidney disease (CKD) in Chinese patients with type 2 diabetes, according to a study in Kidney International.

The study used a new three-stage procedure to test the hypothesis that genetic variants associated with type 2 diabetes, obesity, and fasting plasma glucose might be associated with type 2 diabetes-related CKD. This process was carried out using a large clinicogenomic dataset from a prospective cohort of 2755 patients with type 2 diabetes from the Hong Kong Diabetes Registry.

The model included 25 clinical variables and 36 genetic variants associated with type 2 diabetes, obesity, or fasting plasma glucose. Clinical, genetic, and clinicogenomic models were compared, and the effect of the top selected genetic variants on the clinicogenomic model was assessed. The selected genetic variants were subsequently validated in two independent cohorts.

Of the top six single-nucleotide polymorphisms selected from the clinico- genomic data, three were associated with significant improvement in prediction performance. These were the rs478333 variant of the gene G6PC2 and the rs7754840 and rs7756992 variants of CDKAL1. Patients with the rs478333 variant had a faster decline in eGFR—greater than 4 percent per year. On meta-analysis in replication cohorts, the associations for rs478333 and rs7754840 remained significant after adjustment for conventional risk factors.

The three implicated gene variants seem to be novel predictors of CKD associated with type 2 diabetes in a Chinese population. Jian et al. believe that their three-step process may be useful for selecting predictors of clinical outcomes in other large datasets including clinical and genetic data [Jian G, et al. Genetic and clinical variables identify predictors for chronic kidney disease in type 2 diabetes. Kidney Int 2016; 89:411–420].