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Variants of the adenosine A(2A) receptor gene are protective against proliferative diabetic retinopathy in patients with type 1 diabetes.

ABSTRACT: AIMS: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). CONCLUSION:Genetic variants of ADORA(2A) offer statistically significant protection against PDR development in patients with T1D.

SUBMITTER: Charles BA

PROVIDER: S-EPMC2997447 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Variants of the adenosine A(2A) receptor gene are protective against proliferative diabetic retinopathy in patients with type 1 diabetes.

Charles Bashira A BA Conley Yvette P YP Chen Guanjie G Miller Rachel G RG Dorman Janice S JS Gorin Michael B MB Ferrell Robert E RE Sereika Susan M SM Rotimi Charles N CN Orchard Trevor J TJ

Ophthalmic research 20101119 1

<h4>Aims</h4>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).<h4>Methods</h4>The participants were from the Pittsburgh Epidemiology of Diabetes Complications prospective study of childhood-onset T1D. Stereoscopic photographs of the retinal ...[more]

PMID: 21088442

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Project description:Importance:The comorbidity of chronic kidney disease and diabetic retinopathy (DR) is well known. However, to our knowledge, no cohort study has demonstrated the effect of chronic kidney disease on the development or progression of DR. Objective:To investigate the association of chronic kidney disease with the development of DR and diabetic macular edema (DME) in type 2 diabetes. Design, Setting, and Participants:This 8-year prospective cohort study that was conducted in 2 medical centers in Taiwan included 2135 patients with type 2 diabetes. Exposures:The baseline and mean follow-up renal profiles including serum creatinine level, estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR). Main Outcomes and Measures:Diabetic retinopathy and DME were detected with nonmydriatic fundus photography. Cox regression analyses was used to evaluate the hazard ratios (HRs) for the renal profiles of new-onset DR, proliferative DR, and DME. Results:The mean (SD) age of the study participants was 63.4 (11.9) years and 1025 (48%) were women. A higher serum creatinine level (HR of 2.358 for an increase of 1 mg/dL [to convert to micromoles per liter, multiply by 76.25]; 95% CI, 1.901-2.924; P < .001), an estimated glomerular filtration rate of less than 60 mL/min/1.73m2 (40-60: HR, 2.235; 95% CI, 1.351-4.035; P = .002; 30-45: HR, 2.625; 95% CI, 1.436-4.798; P = .002; <30: HR, 5.488; 95% CI, 2.739-10.993; P < .001), and a urinary albumin to creatinine ratio (ACR) of more than 30 mg/g (31-300: HR, 3.202; 95% CI, 2.029-5.053; P < .001; >300: HR, 6.652; 95% CI, 3.922-11.285; P < .001) at baseline were all associated with the development of proliferative DR. A baseline urinary ACR of more than 30 mg/g (31-300: HR, 1.563; 95% CI, 1.078-2.267; P = .02; >300: HR, 2.707; 95% CI, 1.640-4.470; -2.707; P < 0.001) was associated with the development of DME. After adjusting the baseline values, the mean follow-up renal profiles, including a higher serum creatinine level (HR, 2.369 per mg/dL; 95% CI, 1.704-3.293; P < .001), an estimated glomerular filtration rate of less than 30 mL/min/1.73m2 (HR, 4.215; 95% CI, 1.265-14.039; P = .02), and a urinary ACR of more than 30 mg/g (31-300: HR, 2.344; 95% CI, 1.200-4.503; P = .01; >300: HR, 4.193; 95% CI, 1.638-10.735; P = .003) were still correlated with new-onset PDR during the follow-up periods. Conclusions and Relevance:Abnormal renal profiles at baseline, including a high serum creatinine level, low estimated glomerular filtration rate, and high urinary ACR, were associated with the development of PDR in patients with type 2 diabetes. A high baseline urinary ACR was associated with DME. Abnormal mean follow-up renal profiles were still correlated with new-onset PDR after adjusting for baseline values. Aggressive treatment for chronic kidney disease may have a role in preventing the deterioration of DR.

Dataset Information

Variants of the adenosine A(2A) receptor gene are protective against proliferative diabetic retinopathy in patients with type 1 diabetes.

Publications

Variants of the adenosine A(2A) receptor gene are protective against proliferative diabetic retinopathy in patients with type 1 diabetes.

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