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.
Highlights
posttransplant diabetes mellitus (PTDM) is a common serious complication after kidney transplantation, which is often associated with increased risk of graft failure, cardiovascular disease, and mortality [1]
Eligibility Criteria. e inclusion criteria included (1) kidney transplant recipients diagnosed with new-onset diabetes after transplantation (NODAT) or PTDM according to ADA or WHO guideline, (2) original studies examining the relationship between the gene polymorphism and NODAT or PTDM in patients after kidney transplantation, (3) study type: cohort or case-control studies, and (4) language restricted to English
Genetic factors have been increasingly considered to play an important role in the pathogenesis of PTDM. is metaanalysis showed that gene polymorphisms of TCF7L2 rs7903146, KCNQ1 rs2237892, and KCNJ11 rs5219 contributed to PTDM occurrence and development. e genetic variations of TCF7L2 rs12255372, SLC30A8 rs13266634, PPARc rs1801282, CDKN2A/B rs10811661, HHEX rs1111875, and IGF2BP2 rs4402960 single nucleotide polymorphisms (SNPs) were not found to be associated with PTDM risk
Summary
PTDM is a common serious complication after kidney transplantation, which is often associated with increased risk of graft failure, cardiovascular disease, and mortality [1]. 5.5% to 60.2% of kidney transplant patients develop PTDM in the first year after surgery [2]. Transplantrelated risk factors for PTDM include immunosuppressants, ethnicity, age, sex, body mass index, genetic factors, hepatitis C and cytomegalovirus infections, and family history of diabetes [2]. Immunosuppressive drugs consisting of corticosteroids and calcineurin inhibitors are important risk factors of PTDM, contributing to the development of hyperglycemia and diabetes [4]. Tacrolimus (TAC) and cyclosporin (CsA) are two major calcineurin inhibitors required after transplantation to prevent acute or chronic graft rejections [1]. It has been suggested that glucocorticoid-induced hyperglycemia is partially reversible through avoidance or early withdrawal of the drugs [5]
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