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Mitochondrial DNA haplogroups and risk of new-onset diabetes among tacrolimus-treated renal transplanted patients
Authors:Beatriz Tavira  Juan Gómez  Carmen Díaz-Corte  Laura LLobet  Eduardo Ruiz-Pesini  Francisco Ortega  Eliecer Coto
Institution:1. Genética Molecular, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain;2. Nefrología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain;3. Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain;4. Centro de Investigaciones Biomédicas En Red de Enfermedades Raras (CIBERER), Universidad de Zaragoza, Zaragoza, Spain;5. Fundación Renal I. Alvarez de Toledo, Madrid, Spain;6. Universidad de Oviedo, Oviedo, Spain
Abstract:

Background and aims

Tacrolimus (Tac) is an immunosuppressive drug widely used to avoid organ rejection. New-onset diabetes after transplantation (NODAT) is a major complication among transplanted patients who receive Tac. The increased risk for NODAT could be partly mediated by the effect of Tac on mitochondria from pancreatic beta-cells. Common and rare mitochondrial DNA variants have been linked to the risk of diabetes. Our aim was to determine whether mtDNA polymorphisms/haplogroups were associated with NODAT in Tac-treated kidney transplanted.

Methods

Seven polymorphisms that define the common European haplogroups were determined in 115 NODAT and 197 no-NODAT patients.

Results

Haplogroup H was significantly more frequent in the NODAT group (50% vs. 35%; p = 0.01, OR = 1.82). There was no difference between patients without and with (n = 106) D2M prior to the transplant.

Conclusions

Mitochondrial haplogroup H was associated with the risk for NODAT among Tac-treated transplanted patients. The reported differences between the mtDNA variants could explain the increased NODAT-risk among H-patients.
Keywords:Tac  tacrolimus  DM2  type 2 diabetes  NODAT  new-onset diabetes after transplantation  ROS  reactive oxygen species  OXPHOS  oxidative phosphorylation  mtDNA  mitochondrial DNA  OGTT  oral glucose tolerance test  FPG  fasting plasma glucose  BMI  body mass index
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