title: CCL2 gene polymorphism is associated with post-transplant diabetes mellitus.
abstract: Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, especially in recipients treated with calcineurin inhibitors. Previous studies suggest that chronic inflammation and chemokines play an important role in the pathogenesis of diabetes. Single-nucleotide polymorphisms (SNPs) can increase or decrease transcriptional activity and can change the production of chemokines. The aim of this study was to examine the association between CCL2 and CCL5 gene polymorphisms and the development of post-transplant diabetes mellitus. The study included 315 patients who received kidney transplants and were treated with calcineurin inhibitors. Patients were divided into two subgroups: with PTDM (n=43) and without PTDM (n=272). An additive model of univariate Cox regression analysis showed that the hazard of PTDM development was significantly positively associated with the number of CCL2 rs1024611 G alleles (HR 1.65; 95%CI 1.08-2.53; p=0.021). Multivariate Cox regression analysis, taking into the account the recipient's sex, age and BMI, as well as the number of G alleles of the CCL2 rs1024611 polymorphism, revealed that this polymorphism is an independent risk factor for post-transplant diabetes. The results of our study suggest an association between the CCL2 gene rs1024611 G allele and PTDM in patients treated with tacrolimus or cyclosporine.
authors.affiliation: Department of Pharmacology, Pomeranian Medical University in Szczecin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Dabrowska-Zamojcin
authors.affiliation: Department of General and Transplantation Surgery, Pomeranian Medical University in Szczecin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Romanowski
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Violetta
authors.initials: V
authors.lastname: Dziedziejko
authors.affiliation: Faculty of Physical Education and Health Promotion, University of Szczecin, Szczecin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Maciejewska-Karlowska
authors.affiliation: Faculty of Physical Education and Health Promotion, University of Szczecin, Szczecin, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sawczuk
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.affiliation: Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Domanski
authors.affiliation: Department of Physiology, Pomeranian Medical University, Szczecin, Poland. Electronic address: pawand@poczta.onet.pl.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlik
mesh_terms: D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics; D016572:Cyclosporine / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000235:genetics*; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: C111835:CCL2 protein, human; C483024:CCL5 protein, human; D065095:Calcineurin Inhibitors; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus
keywords: CCL2; CCL5; Graft; Kidney; Polymorphism; Post-transplant diabetes mellitus