title: The -308G>a polymorphism of the TNF gene is associated with proliferative diabetic retinopathy in Caucasian Brazilians with type 2 diabetes.
abstract: OBJECTIVE
  We tested the hypothesis that tumor necrosis factor (TNF) gene polymorphisms are associated with diabetic retinopathy (DR) in Caucasians with type 2 diabetes mellitus.
  
  
  METHODS
  In a case-control study, the -238G>A (rs361525), -308G>A (rs1800629), and -857C>T (rs1799724) polymorphisms of the TNF gene were genotyped in 745 outpatients with type 2 diabetes, including 331 subjects without DR, 246 with nonproliferative DR (NPDR), and 168 with proliferative DR (PDR).
  
  
  RESULTS
  Genotype and allele frequencies of the -238G>A, -308G>A, and -857C>T polymorphisms in subjects with NPDR were not significantly different from those of subjects without DR (P > 0.05 for all comparisons). However, the A allele of the -308G>A polymorphism was more frequent in subjects with PDR than in those with no DR (18.1% vs. 11.5%, corrected P = 0.035). Multivariate logistic regression analysis showed that the -308A allele was independently associated with an increased risk of PDR, under a dominant model (adjusted odds ratio [aOR], 1.82; 95% confidence interval [CI], 1.11-2.98). The combined analysis of the three polymorphisms also showed that haplotypes containing the -308A allele were associated with an increased risk of PDR (aOR, 2.36; 95% CI, 1.29-4.32).
  
  
  CONCLUSIONS
  This study detected, for the first time to our knowledge, an independent association of the -308G>A polymorphism in the TNF gene with PDR in Caucasian Brazilians with type 2 diabetes. This finding suggests that TNF is a potential susceptibility gene for PDR.
authors: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil (ULBRA), Canoas, Brazil.
authors: Luís F C
authors: LF
authors: Sesti
authors: Endocrine Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors: Daisy
authors: D
authors: Crispim
authors: Endocrine Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors: Luís H
authors: LH
authors: Canani
authors: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil (ULBRA), Canoas, Brazil.
authors: Evelise R
authors: ER
authors: Polina
authors: Endocrine Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors: Jakeline
authors: J
authors: Rheinheimer
authors: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil (ULBRA), Canoas, Brazil.
authors: Patrícia S
authors: PS
authors: Carvalho
authors: Endocrine Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors: Jorge L
authors: JL
authors: Gross
authors: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil (ULBRA), Canoas, Brazil Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors: Kátia G
authors: KG
authors: Santos
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D044465:White People
chemical_list: D014409:Tumor Necrosis Factor-alpha; D004247:DNA
keywords: TNF; diabetic retinopathy; polymorphism; type 2 diabetes