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Published on: May 2, 2013
The Association between CDKAL1 Gene rs10946398 Polymorphism and Post-Transplant Diabetes in Kidney Allograft
Violetta Dziedziejko1, Krzysztof Safranow1, Mirosława Kijko-Nowak2
1Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-204 Szczecin, Poland.
Abstract:
Post-transplant diabetes mellitus (PTDM) is a common complication that occurs in kidney transplant patients, increasing the risk of infection, cardiovascular disease and loss of graft function. Currently, factors that increase the risk of this complication are being sought, among them polymorphisms in genes that regulate carbohydrate metabolism and influence pancreatic β-cell function. The aim of this study was to evaluate the association of selected polymorphisms of genes affecting carbohydrate metabolism, such as CDKAL1 rs10946398, GCK rs1799884, GCKR rs780094 and DGKB/TMEM195 rs2191349, with the development of post-transplant diabetes in kidney transplant patients. This study included 201 Caucasian patients after kidney transplantation treated with tacrolimus. An association was observed between the CDKAL1 rs10946398 gene polymorphism and PTDM. Among patients with PTDM, there was an increased prevalence of the CC genotype in the PTDM group compared to the group without PTDM. The chance of PTDM in those with the CC genotype was 2.60 times higher compared to those with the AC + AA genotypes (CC vs. AC + AA OR (95% CI): 2.60 (1.02-6.61), p = 0.040). Multivariate logistic regression analysis showed that advanced age and the CC genotype (rare homozygote) of CDKAL1 rs10946398 were risk factors for the development of PTDM at 1 year after transplantation. There was no statistically significant association between GCK rs1799884, GCKR rs780094 or DGKB/TMEM195 rs2191349 polymorphisms and the development of post-transplant diabetes mellitus in kidney transplant patients. The results of this study suggest that the CDKAL1 rs10946398 CC genotype is associated with the increased risk of PTDM development in patients after kidney graft transplantation treated with tacrolimus.
Insights
The CDKAL1 rs10946398 CC genotype is linked to a higher risk of developing post-transplant diabetes mellitus (PTDM) in kidney transplant patients treated with tacrolimus. Advanced age also emerged as a significant risk factor for PTDM.
Area of Science:
- Nephrology
- Genetics
- Endocrinology
Background:
- Post-transplant diabetes mellitus (PTDM) is a frequent complication following kidney transplantation, associated with increased morbidity and graft dysfunction.
- Identifying genetic factors influencing carbohydrate metabolism may help predict PTDM risk.
Purpose of the Study:
- To investigate the association between specific gene polymorphisms (CDKAL1 rs10946398, GCK rs1799884, GCKR rs780094, DGKB/TMEM195 rs2191349) and the development of PTDM in kidney transplant recipients.
Main Methods:
- A cohort of 201 Caucasian kidney transplant patients treated with tacrolimus was analyzed.
- Genotyping for selected polymorphisms was performed, and associations with PTDM development were assessed using statistical analyses, including logistic regression.
Main Results:
- A significant association was found between the CDKAL1 rs10946398 polymorphism and PTDM. Patients with the CC genotype had a 2.60-fold higher risk of developing PTDM compared to those with AC/AA genotypes (OR: 2.60, 95% CI: 1.02-6.61, p=0.040).
- Multivariate analysis identified advanced age and the CDKAL1 rs10946398 CC genotype as independent risk factors for PTDM at one year post-transplantation.
- No significant associations were observed for GCK rs1799884, GCKR rs780094, or DGKB/TMEM195 rs2191349 polymorphisms with PTDM development.
Conclusions:
- The CDKAL1 rs10946398 CC genotype is a potential genetic marker associated with an increased risk of PTDM in kidney transplant recipients on tacrolimus therapy.
- These findings may contribute to personalized risk assessment and management strategies for PTDM in kidney transplant patients.
Related Concept Videos
Kidney Transplant I: Introduction
Kidney Transplant II: Surgical Procedure

