title: Variants of the adenosine A(2A) receptor gene are protective against proliferative diabetic retinopathy in patients with type 1 diabetes.
abstract: OBJECTIVE
  The adenosine A(2A) receptor (ADORA(2A)) may ameliorate deleterious physiologic effects associated with tissue injury in individuals with diabetes. We explored associations between variants of the ADORA(2A) gene and proliferative diabetic retinopathy (PDR) in a cohort of patients with type 1 diabetes (T1D).
  
  
  METHODS
  The participants were from the Pittsburgh Epidemiology of Diabetes Complications prospective study of childhood-onset T1D. Stereoscopic photographs of the retinal fundus taken at baseline, then biennially, for 10 years were used to define PDR according to the modified Airlie House system. Two tagging single nucleotide polymorphisms (tSNPs; rs2236624-C/T and rs4822489-G/T) in the ADORA(2A) gene were selected using the HapMap (haplotype map) reference database.
  
  
  RESULTS
  A significant association was observed between SNP rs2236624 and PDR in the recessive genetic model. Participants homozygous for the T allele displayed a decreased risk of developing prevalent PDR (odds ratio, OR = 0.36; p = 0.04) and incident PDR (hazard ratio = 0.156; p = 0.009), and for all cases of PDR combined (OR = 0.23; p = 0.001). The protective effect of T allele homozygosity remained after adjusting for covariates. Similarly, for SNP rs4822489, an association between PDR and T allele homozygosity was observed following covariate adjustment (OR = 0.55; 95% CI: 0.31-0.92; p = 0.04).
  
  
  CONCLUSIONS
  Genetic variants of ADORA(2A) offer statistically significant protection against PDR development in patients with T1D.
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USA. charlesba@mail.nih.gov
authors.forename: Bashira A
authors.initials: BA
authors.lastname: Charles
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Miller
authors.forename: Janice S
authors.initials: JS
authors.lastname: Dorman
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gorin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Susan M
authors.initials: SM
authors.lastname: Sereika
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D015861:Retinal Neovascularization / Q000235:genetics* / Q000517:prevention & control; D055815:Young Adult
chemical_list: D043705:Receptor, Adenosine A2A