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.