title: Evaluation of AC(n) and C(-106)T polymorphisms of the aldose reductase gene in Brazilian patients with DM1 and susceptibility to diabetic retinopathy.
abstract: OBJECTIVE
  Diabetic retinopathy (DR) is one of the most important microvascular complications in both type 1 and type 2 diabetes. In Brazil, its proliferative form is the second cause of irreversible blindness among adults of working age. Despite the strong association of DR with disease duration and degree of chronic hyperglycemia, genetic predisposition has been recognized as a possible trigger in the development of this complication. Recent studies have demonstrated that the development of DR in patients with type 1 diabetes is associated with the occurrence of polymorphisms at the 5'-end of the aldose reductase gene (ALR2). There are no reports investigating these polymorphisms in type 1 diabetes Brazilian patients. The aim of this study was to investigate the relationship between the AC(n) repeat and C(-106)T polymorphisms of the ALR2 gene with the susceptibility to the development of DR in Brazilian patients with type 1 diabetes.
  
  
  METHODS
  We selected 64 patients who had diabetes for at least 10 years from Santa Casa de São Paulo and State University of Campinas. The study group was divided into the following: Group 1, patients with no evidence of diabetic retinopathy; group 2, patients with nonproliferative diabetic retinopathy (NPDR); and group 3, patients with proliferative diabetic retinopathy (PDR), confirmed by fundoscopy. The AC(n) microsatellite region was evaluated through polymerase chain reaction (PCR) and automated genotyping and the C(-106)T substitution through polymerase chain reaction/restriction fragment length polymorphism (RFLP).
  
  
  RESULTS
  When each allele of the AC(n) polymorphism was evaluated, the Z allele (24 repeats) was significantly associated with the development of PDR (p=0.014). The C allele of the C(-106)T substitution wasn't associated with the susceptibility to this microvascular complication (p=0.153). When the Z and C allele were concomitantly evaluated regarding their presence or absence a positive correlation was observed for the presence of both alleles and the development of PDR.
  
  
  CONCLUSIONS
  In our sample of Brazilian patients with type 1 diabetes, the presence of the AC(n) polymorphism Z allele may be considered a risk factor for the development of PDR. The C allele of the C(-106)T polymorphism, in association with the Z allele, also increased the risk for the development of PDR, but when it was analyzed by itself there was no association with the complication.
authors.affiliation: Laboratory of Molecular Medicine, Department of Physiology, Faculty of Medical Sciences, Irmandade da Santa Casa de Misericórdia de São Paulo, Brazil
authors.forename: Flávio
authors.initials: F
authors.lastname: Richeti
authors.forename: Renata Maria
authors.initials: RM
authors.lastname: Noronha
authors.forename: Ricardo Temudo Lessa
authors.initials: RT
authors.lastname: Waetge
authors.forename: José Paulo Cabral
authors.initials: JP
authors.lastname: de Vasconcellos
authors.forename: Osías Francisco
authors.initials: OF
authors.lastname: de Souza
authors.forename: Bianca
authors.initials: B
authors.lastname: Kneipp
authors.forename: Nilma
authors.initials: N
authors.lastname: Assis
authors.forename: Mylene Neves
authors.initials: MN
authors.lastname: Rocha
authors.forename: Luís Eduardo Procópio
authors.initials: LE
authors.lastname: Calliari
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Longui
authors.forename: Osmar
authors.initials: O
authors.lastname: Monte
authors.forename: Monica Barbosa
authors.initials: MB
authors.lastname: de Melo
mesh_terms: D000293:Adolescent; D000328:Adult; D000449:Aldehyde Reductase / Q000235:genetics*; D001938:Brazil; D002648:Child; D003596:Cytosine; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013941:Thymine
chemical_list: D003596:Cytosine; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase; D013941:Thymine