KCNQ1 gene variants and risk of new-onset diabetes in tacrolimus-treated renal-transplanted patients

Tavira B, Coto E, Díaz‐Corte C, Ortega F, Arias M, Torres A, Díaz JM, Selgas R, López‐Larrea C, Campistol JM, Ruiz‐Ortega M, Alvarez V, The Pharmacogenetics of Tacrolimus REDINREN Study Group. KCNQ1 gene variants and risk of new‐onset diabetes in tacrolimus‐treated renal‐transplanted patients. Clin Transplant 2011: 25: E284–E291. © 2011 John Wiley & Sons A/S. : Recent genome‐wide association studies identified single‐nucleotide polymorphisms (SNPs) in the gene encoding the pore‐forming subunit of the voltage‐gated K+ channel (KCNQ1) as a risk factor for type 2 diabetes. Tacrolimus (Tac) increased the risk of new‐onset diabetes after transplantation (NODAT). The aim of this study was to analyze the association between KCNQ1 variants and the risk for NODAT in kidney‐transplanted patients who received Tac as primary immunosuppressor. We genotyped three common KCNQ1 SNPs in 145 Spanish patients who received a cadaveric kidney graft and developed NODAT in the first‐year post‐transplant (the NODAT group), and 260 patients who remained non‐diabetics (non‐NODAT). In addition, we searched for DNA variants in the whole KCNQ1 coding exons in these patients. SNP rs2237895 (genotype CC) was associated with an increased risk for NODAT in our population (p = 0.008; OR = 1.83, 95% CI = 1.14–2.93), independently of other risk factors as body mass index, recipient age, or tacrolimus dosage. Other KCNQ1 variants were not associated with NODAT in our patients. Our work supported a role for KCNQ1 gene variants as determinants of the risk of developing NODAT among Tac‐treated patients.