title: Single nucleotide polymorphisms in the Trx2/TXNIP and TrxR2 genes of the mitochondrial thioredoxin antioxidant system and the risk of diabetic retinopathy in patients with Type 2 diabetes mellitus.
abstract: BACKGROUND
  Oxidative stress plays an important role in the pathogenesis of diabetes and its complications. The aim of this study was to examine the possible association between seven single nucleotide polymorphisms (SNPs) of the Trx2/TXNIP and TrxR2 genes encoding proteins involved in the thioredoxin antioxidant defence system and the risk of diabetic retinopthy (DR).
  
  
  METHODS
  Cross-sectional case-control study.
  
  
  METHODS
  A total of 802 Slovenian patients with Type 2 diabetes mellitus; 277 patients with DR and 525 with no DR were enrolled.
  
  
  METHODS
  Patients genotypes of the SNPs; including rs8140110, rs7211, rs7212, rs4755, rs1548357, rs4485648 and rs5748469 were determined by the competitive allele specific PCR method.
  
  
  METHODS
  Each genotype of examined SNPs was regressed in a logistic model, assuming the co-dominant, dominant and the recessive models of inheritance with covariates of duration of diabetes, HbA1c, insulin therapy, total cholesterol and LDL cholesterol levels.
  
  
  RESULTS
  In the present study, for the first time we identified an association between the rs4485648 polymorphism of the TrxR2 gene and DR in Caucasians with Type 2 DM. The estimated ORs of adjusted logistic regression models were found to be as follows: 4.4 for CT heterozygotes, 4.3 for TT homozygotes (co-dominant genetic model) and 4.4 for CT+TT genotypes (dominant genetic model).
  
  
  CONCLUSIONS
  In our case-control study we were not able to demonstrate any association between rs8140110, rs7211, rs7212, rs4755, rs1548357, and rs5748469 and DR, however, our findings provide evidence that the rs4485648 polymorphism of the TrxR2 gene might exert an independent effect on the development of DR.
authors.affiliation: Institute of Histology and Embriology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Sara Mankoc
authors.initials: SM
authors.lastname: Ramus
authors.affiliation: Institute of Histology and Embriology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Ines
authors.initials: I
authors.lastname: Cilensek
authors.affiliation: University Medical Centre, Eye Clinic, Ljubljana, Slovenia.
authors.forename: Mojca Globocnik
authors.initials: MG
authors.lastname: Petrovic
authors.affiliation: 2(nd) Department of Internal Medicine, St. Anne´s University Hospital and Masaryk University, Brno, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Soucek
authors.affiliation: Laboratory of Structural Biology and Proteomics, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic. Electronic address: kruzliakpeter@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Institute of Histology and Embriology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia. Electronic address: daniel.petrovic@mf.uni-lj.si.
authors.forename: Daniel
authors.initials: D
authors.lastname: Petrovic
mesh_terms: D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D054482:Thioredoxin Reductase 2 / Q000235:genetics*; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D024101:Mitochondrial Proteins; C467002:TXN2 protein, human; C486715:TXNIP protein, human; D013879:Thioredoxins; C516127:TXNRD2 protein, human; D054482:Thioredoxin Reductase 2
keywords: Diabetic retinopathy; Oxidative stress; Single nucleotide polymorphism; Thioredoxin antioxidant system; Type 2 diabetes mellitus