title: Association of genetic polymorphisms of angiopoietin-like 4 with severity of posttransplant proteinuria in kidney allograft recipients.
abstract: Proteinuria is a hallmark of glomerular injury, and persistent proteinuria is associated with graft failure in kidney transplant patients. Recently, it is known that the level of circulating angiopoietin-like 4 (ANGPTL4) is elevated in the patients with human nephrotic syndrome, in which ANGPTL4 is responsible for relieving proteinuria.
  
  
  
  The purpose of this study is to determine effects of clinical factors and genetic polymorphism of ANGPTL4 on proteinuria after kidney transplantation.
  
  
  
  A total of 282 patients out of 400 renal transplant patients between 2008 and 2012 at St. Vincent Medical Center, CA were studied in a retrospective study design. The level of proteinuria was measured by random urine protein to creatinine ratio, and divided into two groups (Group 1: UPC<500mg/day, Group 2: ≥500mg/day). Single nucleotide polymorphisms of ANGPTL4 genes (rs1044250, rs2278236, rs116843064, rs11672433, rs4076317) were determined by real time PCR with sequence specific primers.
  
  
  
  Among various clinical factors, only delayed graft function, mTOR inhibitor use and fish oil use were significantly associated with posttransplant proteinuria. Statistical differences were found in genetic polymorphisms of ANGPTL4 (rs1044250, rs2278236) in regards to proteinuria among tested patients. rs1044250 (C/T, T228M, missense mutation) alleles showed multiple significant differences (Group 1 vs. Group 2: C vs. T: OR=1.893, CI=1.322-2.710, p<0.001). Similar trends were found in rs2278236 (A/G) alleles with statistical significances (Group 1 vs. Group 2: A vs. G: OR=0.620, CI=0.443-0.867, p=0.005). With multiple logistic regression, rs1044250 was still a significant risk factor of moderate/severe proteinuria (p=0.021).
  
  
  
  This study suggests that the presence of C allele of rs1044250 and G allele of rs2278236 in ANGPTL4 gene is associated with higher risk of moderate/severe proteinuria in renal transplant patients.
authors.affiliation: Mendez National Institute of Transplantation, Los Angeles, CA, United States; Western University of Health Sciences, Pomona, CA, United States.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Mendez National Institute of Transplantation, Los Angeles, CA, United States; Western University of Health Sciences, Pomona, CA, United States; St. Vincent Medical Center, Los Angeles, CA, United States.
authors.forename: Tariq
authors.initials: T
authors.lastname: Shah
authors.affiliation: Sahmyook University, Seoul, Republic of Korea.
authors.forename: Jaewook
authors.initials: J
authors.lastname: Yang
authors.affiliation: Western University of Health Sciences, Pomona, CA, United States. Electronic address: dmin@westernu.edu.
authors.forename: David I
authors.initials: DI
authors.lastname: Min
mesh_terms: D064591:Allografts / Q000502:physiology*; D000075803:Angiopoietin-Like Protein 4 / Q000235:genetics*; D003404:Creatinine / Q000652:urine; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics*; D012189:Retrospective Studies; D012306:Risk; D014184:Transplantation, Homologous
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D003404:Creatinine
keywords: ANGPTL4; Angiopoietin-like 4; Genetic polymorphisms; Kidney transplantation; Proteinuria