期刊
OPHTHALMIC RESEARCH
卷 46, 期 1, 页码 1-8出版社
KARGER
DOI: 10.1159/000317057
关键词
Diabetes; Diabetic retinopathy; Single nucleotide polymorphism; Adenosine receptor
资金
- NIH/National Institute of Nursing Research [1F31NR008970-01A2]
- American Nurses Foundation
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK034818-21]
- National Human Genome Research Institute, NIH, in the Center for Research in Genomics and Global Health [Z01HG200362]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000005] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [Z01HG200362] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK034818] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NURSING RESEARCH [F31NR008970] Funding Source: NIH RePORTER
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. Copyright (C) 2010 S. Karger AG, Basel
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