title: Genetic variants in ICAM1, PPARGC1A and MTHFR are potentially associated with different phenotypes of diabetic retinopathy.
abstract: OBJECTIVE
  To explore phenotype-genotype correlations that may contribute to a better understanding of diabetic retinopathy (DR).
  
  
  METHODS
  An exploratory association study was performed to identify genetic variants associated with non-proliferative DR (NPDR) in 307 type 2 diabetic patients who were previously stratified into 3 different phenotypes of NPDR progression. The 307 patients were genotyped for 174 single nucleotide polymorphisms of 11 candidate genes (ACE, AGER, AKR1B1, ICAM1, MTHFR, NOS1, NOS3, PPARGC1A, TGFB1, TNF and VEGFA).
  
  
  RESULTS
  Significant associations were observed for PPARGC1A rs16874120 with phenotype A (odds ratio, OR = 0.60, 95% confidence interval, CI 0.36-0.99), ICAM1 rs1801714 with phenotype B (OR = 3.32, 95% CI 1.05-10.50) and both PPARGC1A rs10213440 (OR = 2.00, 95% CI 1.07-3.73) and MTHFR rs1801133 (OR = 1.84, 95% CI 1.08-3.11) with phenotype C.
  
  
  CONCLUSIONS
  RESULTS indicate that specific gene variants in ICAM1, PPARGC1A and MTHFR are associated with different NPDR phenotypes, being likely candidates to explain different disease mechanisms underlying the different phenotypes. This is the first study to show correlations between specific gene variants and NPDR phenotypes, opening new perspectives on DR.
authors.affiliation: Genoinseq, Next Generation Sequencing Unit, Biocant, Cantanhede, Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Simões
authors.forename: Conceição
authors.initials: C
authors.lastname: Lobo
authors.forename: Conceição
authors.initials: C
authors.lastname: Egas
authors.forename: Sandrina
authors.initials: S
authors.lastname: Nunes
authors.forename: Susana
authors.initials: S
authors.lastname: Carmona
authors.forename: Miguel Ângelo
authors.initials: MÂ
authors.lastname: Costa
authors.forename: Tânia
authors.initials: T
authors.lastname: Duarte
authors.forename: Luísa
authors.initials: L
authors.lastname: Ribeiro
authors.forename: Carlos
authors.initials: C
authors.lastname: Faro
authors.forename: José G
authors.initials: JG
authors.lastname: Cunha-Vaz
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C573420:ICAM1 protein, human; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D018799:Intercellular Adhesion Molecule-1; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)