Association between Angiotensin I-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of Kidney Transplantation: A Meta-Analysis

Purpose Angiotensin I-converting enzyme (ACE) is crucial in the renin–angiotensin–aldosterone system. ACE insertion/deletion (I/D) polymorphism is a common genetic variation of this gene and is associated with several disease phenotypes. However, the results of published studies on the influence of this polymorphism on renal transplantation are inconsistent. Therefore, a meta-analysis was performed to evaluate the association between ACE I/D polymorphism and prognosis of kidney transplantation. Methods A meta-analysis was performed based on 21 case–control studies from 12 publications (1497 cases and 2029 controls) and 10 studies with quantitative values from 5 publications (814 patients). Pooled odds ratios (ORs) and weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were used to estimate associations. Results ACE I/D polymorphism was found to be associated with acute rejection (AR) in genotypes DD+ID versus II (OR = 1.62, 95% CI = 1.14–2.29) and with serum creatinine concentration after renal transplantation in genotypes DD versus ID (WMD = 13.12, 95% CI = 8.09–18.16). Stratified analysis revealed that recipients transplanted within a year had higher serum creatinine concentrations in the DD versus ID model. No significant association was found between hypertension and ACE I/D polymorphism. Conclusion ACE I/D polymorphism is associated with AR and allograft function after kidney transplantation.

[1]  L. Lara,et al.  Renin-angiotensin system in the kidney: What is new? , 2014, World journal of nephrology.

[2]  R. Vanholder,et al.  Genotypes of renin-angiotensin system and plasma adiponectin concentration in kidney transplant patients. , 2013, Annals of transplantation.

[3]  T. Zhu,et al.  Soluble FGL2 induced by tumor necrosis factor-α and interferon-γ in CD4+ T cells through MAPK pathway in human renal allograft acute rejection. , 2013, The Journal of surgical research.

[4]  Sean Ennis,et al.  A genome‐wide association study of recipient genotype and medium‐term kidney allograft function , 2013, Clinical transplantation.

[5]  N. Câmara,et al.  Clinical impact of an angiotensin I-converting enzyme insertion/deletion and kinin B2 receptor +9/-9 polymorphisms in the prognosis of renal transplantation , 2013, Biological chemistry.

[6]  J. Chudek,et al.  Association between gene polymorphisms of the components of the renin-angiotensin-aldosteron system, graft function, and the prevalence of hypertension, anemia, and erythrocytosis after kidney transplantation. , 2011, Transplantation proceedings.

[7]  A. Tóth,et al.  Insertion/deletion polymorphism of the angiotensin-converting enzyme predicts left ventricular hypertrophy after renal transplantation. , 2011, Transplantation proceedings.

[8]  H. Kobori,et al.  Intrarenal angiotensin II and its contribution to the genesis of chronic hypertension. , 2011, Current opinion in pharmacology.

[9]  A. Tóth,et al.  Insertion/Deletion polymorphism of Angiotensin-converting enzyme as a risk factor for chronic allograft nephropathy. , 2010, Transplantation proceedings.

[10]  A. McDonough.  Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure. , 2010, American journal of physiology. Regulatory, integrative and comparative physiology.

[11]  J. Probstfield,et al.  Progression of cardiovascular damage: the role of renin-angiotensin system blockade. , 2010, The American journal of cardiology.

[12]  M. Loh,et al.  Impact of genetic polymorphisms of the renin–angiotensin system and of non‐genetic factors on kidney transplant function – a single‐center experience , 2009, Clinical transplantation.

[13]  Guojun Wu,et al.  Gene polymorphisms of the renin-angiotensin-aldosterone system and angiotensin II type 1-receptor activating antibodies in renal rejection. , 2007, The Tohoku journal of experimental medicine.

[14]  H. Argani,et al.  Renin-angiotensin system polymorphisms and renal graft function in renal transplant recipients. , 2007, Saudi medical journal.

[15]  H. Argani,et al.  Enalapril and losartan affect lipid peroxidation in renal transplant recipients with renin-angiotensin system polymorphisms. , 2007, Clinical biochemistry.

[16]  E. Serdaroğlu,et al.  Hypertension and ace gene insertion/deletion polymorphism in pediatric renal transplant patients , 2005, Pediatric transplantation.

[17]  K. Safranow,et al.  The influence of angiotensin-converting enzyme gene of donor and recipient on the function of transplanted kidney. , 2005, Transplantation proceedings.

[18]  M. Haberal,et al.  Association of the Genetic Polymorphisms of the Renin-Angiotensin System and Endothelial Nitric Oxide Synthase With Chronic Renal Transplant Dysfunction , 2004, Transplantation.

[19]  G. Boivin,et al.  An ACE inhibitor reduces Th2 cytokines and TGF-β1 and TGF-β2 isoforms in murine lupus nephritis , 2004 .

[20]  J. Egido,et al.  Inflammation and angiotensin II. , 2003, The international journal of biochemistry & cell biology.

[21]  Marta Ruiz-Ortega,et al.  Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. , 2002, Kidney international. Supplement.

[22]  M. Sever,et al.  The effect of angiotensin converting enzyme gene polymorphism on chronic allograft dysfunction in living donor renal transplant recipients , 2002, Clinical transplantation.

[23]  F. Berthou,et al.  Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1 R and ecNOS. , 2002, Clinical nephrology.

[24]  B. Fellström.  Nonimmune risk factors for chronic renal allograft disfunction. , 2001, Transplantation.

[25]  H. Neumayer,et al.  Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients , 2001, Pediatric transplantation.

[26]  J. Pitha,et al.  ACE gene polymorphism and long-term renal graft function. , 2001, Clinical biochemistry.

[27]  B. Antus,et al.  Effect of angiotensin-converting enzyme inhibition on growth factor mRNA in chronic renal allograft rejection in the rat. , 2000, Kidney international.

[28]  M. Rieder,et al.  Sequence variation in the human angiotensin converting enzyme , 1999, Nature Genetics.

[29]  D. Zeeuw,et al.  Risk factors for long-term renal survival after renal transplantation: a role for angiotensin-converting enzyme (insertion/deletion) polymorphism? , 1998, Journal of the American Society of Nephrology : JASN.

[30]  A. Distler,et al.  Role of genetic variants of the renin-angiotensin system in chronic renal allograft injury. , 1998, Kidney international.

[31]  J P Vandenbroucke,et al.  Bias in meta-analysis detected by a simple, graphical test , 1998 .

[32]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[33]  S. Engeli,et al.  Angiotensin-converting enzyme genotype and renal allograft survival. , 1997, Journal of the American Society of Nephrology : JASN.

[34]  E. Salido,et al.  Prediction of left ventricular mass changes after renal transplantation by polymorphism of the angiotensin-converting-enzyme gene. , 1997, Kidney international.

[35]  D. Rush,et al.  Report of the Third Banff Conference on Allograft Pathology (July 20-24, 1995) on classification and lesion scoring in renal allograft pathology. , 1996, Transplantation proceedings.

[36]  T. Hostetter,et al.  Chronic transplant rejection. , 1994, Kidney international.

[37]  P Corvol,et al.  An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. , 1990, The Journal of clinical investigation.

[38]  W. G. Cochran.  The comparison of percentages in matched samples. , 1950, Biometrika.

[39]  G. Boivin,et al.  An ACE inhibitor reduces Th2 cytokines and TGF-beta1 and TGF-beta2 isoforms in murine lupus nephritis. , 2004, Kidney international.

[40]  L. Rubenstein,et al.  Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. , 1998, BMJ.

[41]  J. T. Lumeij,et al.  Avian Clinical Biochemistry , 1997 .

[42]  A. Distler,et al.  Nephrology Dialysis Transplantation Angiotensin-converting-enzyme Insertion/deletion Genotype and Long-term Renal Allograft Survival , 2022 .