Genetic Variations in a Sestrin2/Sestrin3/mTOR Axis and Development of New-Onset Diabetes After Transplantation.

Abstract

Background: Genetic variations in Sestrin2/Sestrin3/ mTOR axis may cause obesity-associated metabolic syndrome, including lipid accumulation and insulin resistance, and then increase the individual's risk of diabetes. Accordingly, we explored the association between single nucleotide polymorphisms (SNPs) of these genes and new-onset diabetes after transplantation (NODAT) in our Hispanic kidney transplant recipients. Methods: We genotyped 8 potential functional polymorphisms in Sestrin2, Sestrin3 and mTOR genes using the Taqman method in a study of 129 Hispanic RTRs with no evidence of pre-existing diabetes who developed NODAT and 186 controls with no history of diabetes. The Cox proportional hazard model was used to examine risk factor for NODAT. Nongenetic and genetic characteristics were included in the multivariate risk model. Results: We observed significant associations between NODAT and mTOR rs2295080 TT (OR=1.6, 95% CI =1.14-2.82, p=0.01), Sestrin2 rs580800 AA (OR=0.42, 95% CI =0.27-0.67, p=0.0002), and Sestrin3 rs684856 AA (OR=0.45, 95% CI=0.27-0.75, p=0.001). There was an interaction between the mTOR rs2295080 and Sestrin3 rs684856 and risk of NODAT (p interaction = 0.046). Of the non-genetic factors, use of tacrolimus, older age, and acute rejection were associated with increased risk for NODAT. Conclusion: Polymorphism in the Sestrin2/Sestrin3/mTOR gene may confer certain protection or predisposition for NODAT