The role of TCF7L2 rs7903146 in diabetes after kidney transplant: Results from a single-center cohort and meta-analysis of the literature

Background. Several genetic polymorphisms modulate the risk of posttransplant diabetesmellitus (PTDM), a complication associated with an increased morbidity and mortality after kidney transplantation; however, their clinical utility is still undefined. Methods. Genetic analysis was performed in 464 kidney transplantation recipients to evaluate whether transcription factor 7-like 2 (TCF7L2) rs7903146 gene polymorphism is associated with the risk of PTDMand ameta-analysis of similar studies including our results was performed (total kidney transplantation recipients, n = 3105). A predictivemodel of PTDMwas built on the basis of this polymorphism and clinical parameters. Results. In our cohort, 163 patients possessed the CC genotype of rs7903146 (35.1%), 237 were CT (51.1%), and 64 were TT (13.8%): their 2 years PTDM incidence was, respectively, 7.8%, 11.9%, and 22.7%. At multivariate analysis, age (per year; hazard ratio [HR], 1.029; 95% confidence interval [95% CI], 1.005-1.054; P = 0.017), body mass index (25.0-29.9 vs <25.0; HR, 2.43; 95% CI, 1.40-4.23; P = 0.0018; ≥30 vs <25.0; HR, 5.70; 95% CI, 2.77-11.74; P < 0.0001), TCF7L2 rs7903146 (per each Tallele; HR, 1.81; 95% CI, 1.26-2.59; P = 0.001) and previous transplants (HR, 2.80; 95% CI, 1.39-5.64; P = 0.004) emerged as independent predictive factors for PTDM. Meta-analysis of present and 5 previous studies showed higher risk of PTDM in carriers of rs7903146 TT genotype (odds ratio, 1.95; 95% CI, 1.39-2.74; P < 0.0001) and absence of heterogeneity among studies (I2 = 0%). Inclusion of this polymorphism in a predictivemodel appeared to improve its ability to stratify patients according to the risk of PTDM. Conclusions. In renal transplant patients, TCF7L2 rs7903146 is strongly and independently associated with PTDM and might hold the potential to identify patients at risk for this complication.