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Association between E23K variant in KCNJ11 gene and new-onset diabetes after liver transplantation

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Abstract

New-onset diabetes after transplantation (NODAT) is an important complication after solid organ transplantation. NODAT is a polygenic disease and KCNJ11 E23K polymorphism is considered as a diabetes-susceptibility gene. The present study aimed to assess the association between KCNJ11 (rs5219) variants and the risk of developing NODAT after liver transplantation. This study was conducted on 120 liver transplant recipients who had received tacrolimus-based immunosuppressive drugs. The liver transplant recipients were divided into an new onset diabetes mellitus (NODM) and a non-NODM group. The NODAT group consisted of 60 patients who developed diabetes in the first 6 months after transplantation, while the non-NODAT group included 60 patients who remained euglycemic. The patients were genotyped using polymerase chain reaction–restriction fragment length polymorphism and the incidence of NODAT was compared between the two groups. Nongenetic risk factors including donor gender and cold ischemia time, and recipient (MELD score, presence of viral hepatitis, acute rejection and steroid pulse therapy) were also considered. The KCNJ11 KK variant was associated with an increased risk for NODAT with respective odds ratio of 6.03 (95 % confidence interval 2.37–15.4; P < 0.001]. Donor age and male sex, recipient age as well as fasting plasma glucose before transplantation were significantly different between NODAT and non-NODAT groups (P < 0.05). The prednisolone daily dosage was significantly higher in the NODAT group (P = 0.01). These patients received pulse of methyl prednisolone for treatment of acute rejection. This study showed that polymorphisms in KCNJ11 might predispose the patients treated by tacrolimus to development of NODAT after liver transplantation.

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Acknowledgments

The present article was extracted from Zahra Parvizi’s M. Sc. thesis in cellular developmental biology. Hereby, the authors would like to thank Organ Transplant Research Center of Nemazee Hospital for their assistance in performance of this project. They are also grateful for Ms. A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for improving the use of English in the manuscript.

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Authors and Affiliations

  1. Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Zand Street, 7193711351, Shiraz, Iran

    Zahra Parvizi, Negar Azarpira, Leila Kohan & Masumeh Darai

  2. Department of Biology, Faculty of Science, Islamic Azad University, Arsenjan, Iran

    Zahra Parvizi & Leila Kohan

  3. Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Kourosh Kazemi

  4. Traditional Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohamad Mehdi Parvizi

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  1. Zahra Parvizi
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Correspondence to Negar Azarpira.

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Parvizi, Z., Azarpira, N., Kohan, L. et al. Association between E23K variant in KCNJ11 gene and new-onset diabetes after liver transplantation. Mol Biol Rep 41, 6063–6069 (2014). https://doi.org/10.1007/s11033-014-3483-0

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