Association between Genetic Polymorphisms and Risk of Kidney Posttransplant Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract

Objectives. The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk. Methods. Relevant publications were systematically retrieved from PubMed, EMBASE, and the Cochrane Library up to December 2020. Data from eligible case-control and cohort studies were extracted for qualitative and quantitative analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between gene polymorphisms and PTDM in the quantitative meta-analysis. Results. A total of 43 eligible articles were identified, and 16 studies on 9 DNA variants from 8 genes were included in the meta-analysis. TCF7L2 rs7903146 was significantly associated with PTDM risk in 5 genetic models (OR (95% CI): allelic: 1.59 (1.17–2.16), P = 0.003 ; dominant recessive: 1.62 (1.14, 2.31), P = 0.007 ; recessive: 1.87 (1.18, 2.94), P = 0.007 ; homozygote: 2.21 (1.23, 3.94), P = 0.008 ; and heterozygote 1.50 (1.08, 2.10), P = 0.017 ). KCNQ1 rs2237892 was significantly correlated with PTDM risk in 3 genetic models (allelic: 0.68 (0.58, 0.81), P < 0.001 ; dominant: 0.6 (049, 0.74), P < 0.001 ; and heterozygote: 0.61 (0.48, 0.76), P < 0.001 ). KCNJ11 rs5219 was significantly linked with PTDM in the recessive genetic model (1.59 (1.01, 2.50), P = 0.047 ). No significant correlations of PTDM with TCF7L2 rs12255372, SLC30A8 rs13266634, PPARγ rs1801282, CDKN2A/B rs10811661, HHEX rs1111875, and IGF2BP2 rs4402960 polymorphisms were found. Conclusions. The gene polymorphisms of TCF7L2 rs7903146, KCNQ1 rs2237892, and KCNJ11 rs5219 may predispose kidney transplant recipients to PTDM. Large sample size studies on diverse ethnic populations were warranted to confirm our findings.

The Association between CDKAL1 Gene rs10946398 Polymorphism and Post-Transplant Diabetes in Kidney Allograft Recipients Treated with Tacrolimus

“…PTDM occurs frequently after kidney transplantation and may be associated with graft loss, so factors that may increase the risk of this complication are being sought. Previous studies have shown that the pathophysiological changes leading to the development of PTDM are similar to those in type 2 diabetes mellitus [ 7 , 8 , 22 , 23 ]. It is believed that the risk factors leading to the occurrence of PTDM include factors associated with the development of type 2 diabetes mellitus, such as obesity, metabolic syndrome and a family history of type 2 diabetes mellitus.…”

“…Underlying this complication are factors affecting carbohydrate metabolism and pancreatic function, including genetic conditions. To date, many studies have considered the role of genetic polymorphisms as risk factors for the development of PTDM [ 8 ]. In particular, polymorphisms that have been confirmed to be associated with type 2 diabetes have been taken into account.…”

“…Among them are polymorphisms in genes encoding enzymes involved in carbohydrate metabolism. To date, many of the genes responsible for the development of type 2 diabetes have also been shown to be associated with an increased risk of post-transplant diabetes [ 8 ].…”

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus

“…There is some evidence of a genetic predisposition to PTDM, including established associations with the alleles HLA A28, A30, B27, and Bw42. Furthermore, a report has emphasized the association of TCF7L2 rs7903146 and SLC30A8 rs13266634 polymorphisms with a higher risk of PTDM [42][43][44][45]. Another study investigated the association of genetics with PTDM in a white UK renal transplant population; 26 SNPs were associated with PTDM, such as ATP5F1P6 rs1048482, DNAJC16 rs7533125, and CELA2B rs2861484 [46].…”