Bruna B Nicoletto1, Gabriela C Souza, Natasha K O Fonseca, Analaura Centenaro, Roberto C Manfro, Luís Henrique S Canani, Luiz Felipe Santos Gonçalves. 1. 1 Post Graduation Medicine Program: Medical Sciences, School of Medicine, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. 2 Nutrition Course, School of Medicine, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. 3 Division of Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 4 Post Graduation Medical Sciences Program: Endocrinology, School of Medicine, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. 5 Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 6 Department of Internal Medicine, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. 7 Address correspondence to: Luiz Felipe Santos Gonçalves, M.D., Ph.D., Division of Nephrology, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos Street, Room 2030, ZIP code 90035-903 Porto Alegre, Brazil.
Abstract
BACKGROUND: New-onset diabetes after transplantation (NODAT) is a well-recognized complication of kidney transplantation and is associated with poor outcomes. Both adiponectin and chemokine ligand 5 (CCL5) proteins are related to glucose metabolism and genetic variations in their genes can lead to development of NODAT. The aim of this study was to investigate the association of adiponectin and CCL5 genes polymorphisms with NODAT in a population of Caucasian kidney transplant recipients. METHODS: Two hundred seventy Caucasian kidney transplant recipients (83 with NODAT and 187 without NODAT) were included in a nested case-control study. Patients with pretransplantation diabetes mellitus and multiorgan transplantation were excluded. NODAT diagnosis was determined by American Diabetes Association criteria. Subjects were genotyped for 276G/T adiponectin gene polymorphism (rs1501299) and rs2280789 and rs3817655 CCL5 gene polymorphisms by real-time polymerase chain reaction. RESULTS: The TT genotype of 276G/T adiponectin gene polymorphism was significantly more frequent in NODAT than non-NODAT patients compared with GG/GT genotypes (recessive model; P=0.031). TT genotype was identified as an independent risk factor for NODAT in Caucasian kidney transplant recipients after adjusting for age at transplantation, pretransplantation body mass index, and use of tacrolimus (TT vs. GG/GT, hazard ratio=1.88, 95% confidence interval=1.03-3.45, P=0.041). There were no differences in genotype distribution and allele frequency of rs2280789 and rs3817655 CCL5 gene polymorphisms between NODAT and non-NODAT groups. CONCLUSIONS: The 276G/T adiponectin gene polymorphism is associated with NODAT in Caucasian kidney transplant recipients.
BACKGROUND: New-onset diabetes after transplantation (NODAT) is a well-recognized complication of kidney transplantation and is associated with poor outcomes. Both adiponectin and chemokine ligand 5 (CCL5) proteins are related to glucose metabolism and genetic variations in their genes can lead to development of NODAT. The aim of this study was to investigate the association of adiponectin and CCL5 genes polymorphisms with NODAT in a population of Caucasian kidney transplant recipients. METHODS: Two hundred seventy Caucasian kidney transplant recipients (83 with NODAT and 187 without NODAT) were included in a nested case-control study. Patients with pretransplantation diabetes mellitus and multiorgan transplantation were excluded. NODAT diagnosis was determined by American Diabetes Association criteria. Subjects were genotyped for 276G/T adiponectin gene polymorphism (rs1501299) and rs2280789 and rs3817655CCL5 gene polymorphisms by real-time polymerase chain reaction. RESULTS: The TT genotype of 276G/T adiponectin gene polymorphism was significantly more frequent in NODAT than non-NODAT patients compared with GG/GT genotypes (recessive model; P=0.031). TT genotype was identified as an independent risk factor for NODAT in Caucasian kidney transplant recipients after adjusting for age at transplantation, pretransplantation body mass index, and use of tacrolimus (TT vs. GG/GT, hazard ratio=1.88, 95% confidence interval=1.03-3.45, P=0.041). There were no differences in genotype distribution and allele frequency of rs2280789 and rs3817655CCL5 gene polymorphisms between NODAT and non-NODAT groups. CONCLUSIONS: The 276G/T adiponectin gene polymorphism is associated with NODAT in Caucasian kidney transplant recipients.