title: Genetic polymorphisms located in TGFB1, AGTR1, and VEGFA genes are associated to chronic renal allograft dysfunction.
abstract: BACKGROUND
  Persistent inflammation and fibrosis have been related to active progression of renal deterioration and reduced survival of kidney transplant. The aim of this study was to determine the impact of single-nucleotide polymorphisms (SNPs) located in regions related to inflammatory and immune processes on the development of chronic renal allograft dysfunction (CRAD).
  
  
  METHODS
  A retrospective study was carried out on 276 patients who received kidney transplant (KT). SNPs were genotyped via the SNPlex platform. Statistical analysis was performed with SNPstat and regression logistic analyses were adjusted by age and gender of recipients and donors, cold ischemia time and the number of human leukocyte antigen (HLA) mismatches.
  
  
  RESULTS
  From 276 patients with KT, 118 were non-CRAD and 158 were CRAD. Three SNPs showed significant associations with CRAD development: rs1800471 in transforming growth factor beta 1 (TGFB1), rs5186 in angiotensin II receptor type 1 (AGTR1), and rs699947 in vascular endothelial growth factor A (VEGFA). GC genotype of rs1800471 was associated with increased odds of CRAD compared to GG genotype (OR=2.65 (95% confidence interval (CI)=1.09; 6.47), p=0.025), as well as AC and AA genotype of rs699947 assuming a dominant model (OR=1.80 (95% CI=1.02; 3.20), p=0.044). Besides, AC and CC genotypes of rs5186 were associated with reduced odds of CRAD assuming a dominant model (OR=0.56 (95% CI=0.33; 0.96), p=0.033).
  
  
  CONCLUSIONS
  Our findings suggest that three genes related to immunity and inflammation (rs1800471, rs5186 and rs699947) are associated to susceptibility or protection to CRAD, and might have diagnostic utility in predicting the likelihood of developing CRAD.
authors.affiliation: Unidad de Epidemiología Molecular de Enfermedades Infecciosas, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: María
authors.initials: M
authors.lastname: Heredia
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tamayo
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: Carmen
authors.initials: C
authors.lastname: Lajo
authors.forename: Elisabeth
authors.initials: E
authors.lastname: López
authors.forename: José I
authors.initials: JI
authors.lastname: Gómez-Herreras
authors.forename: Jesús
authors.initials: J
authors.lastname: Bustamante
authors.forename: Jesús F
authors.initials: JF
authors.lastname: Bermejo-Martín
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012189:Retrospective Studies; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A