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Lucia Sobrin, Todd Green, Xueling Sim, Tay W. Ting, Richard A. Jensen, Barbara E. Klein, Mary Frances Cotch, Ronald Klein, Mark J. Daly, Tien Y. Wong; Candidate Gene Study for Diabetic Retinopathy in CARe. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2097.
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To investigate whether variants in genes linked to diabetes, diabetic nephropathy, and cardiovascular disease are associated with diabetic retinopathy (DR) in a consortium of population-based cohorts.
In the Candidate Gene Association Resource (CARe) study, 1746 European Americans with type 2 diabetes (T2D) had fundus photographs graded for DR by the Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria and were genotyped for 49,320 single nucleotide polymorphisms (SNPs) from approximately 2,000 diabetes and cardiovascular-related candidate genes. Two definitions of DR cases were investigated: any DR (ETDRS grade ≥ 14) and moderate DR (ETDRS grade ≥ 30). For all analyses, controls were defined as having no DR (ETDRS grade < 14). Independent chi-square analysis in each cohort were combined by Cochran-Mantel-Haenszel pooling of the odds ratios (ORs) and corrected for multiple hypothesis testing using Bonferroni and permutation methods. For all statistically significant associations, logistic regression was performed adjusting for age, duration of diabetes, fasting glucose, total cholesterol, systolic and diastolic blood pressure. All statistical analyses were performed using PLINK.
Among 39 genes that have previously been associated with DR, diabetic nephropathy or T2D, three SNPs in the P selectin gene (SELP) were associated with any DR after correction for multiple testing including Bonferroni and permutation testing. The strongest association was to rs6128 (OR=0.55, p= 0.00636 and p=0.0003, respectively). All three SNPs remained significantly associated after adjusting for other known risk factors for DR. In addition, a variant on chromosome 4, rs6856425, was associated with any DR (OR=2.98, p=1.87 X 10-6 ) and moderate DR (OR=4.15, p=4.80 X 10-8). Only the association with moderate DR remained significant after correction by Bonferroni and permutation testing (p=0.00116 and 0.0087, respectively) and logistic regression (OR=4.87, p=0.002).
Genetic variants in SELP and on chromosome 4 are associated with DR in CARe.
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