title: Association between E23K variant in KCNJ11 gene and new-onset diabetes after liver transplantation.
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.
authors.affiliation: Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Zand Street, 7193711351, Shiraz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Parvizi
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.forename: Leila
authors.initials: L
authors.lastname: Kohan
authors.forename: Masumeh
authors.initials: M
authors.lastname: Darai
authors.forename: Kourosh
authors.initials: K
authors.lastname: Kazemi
authors.forename: Mohamad Mehdi
authors.initials: MM
authors.lastname: Parvizi
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001786:Blood Glucose; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; C086989:KCNJ1 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D016559:Tacrolimus