@article {1003, title = {Apolipoprotein E gene and retinal microvascular signs in older people: the Cardiovascular Health Study.}, journal = {Mol Vis}, volume = {13}, year = {2007}, month = {2007 Nov 12}, pages = {2105-11}, abstract = {

PURPOSE: To examine the association between apolipoprotein E (APOE) gene polymorphism and retinal microvascular signs in an older population.

METHODS: Retinal photographs were taken of 2,152 participants (1,831 whites, and 321 African-Americans), aged 69-96 years, who were participating in a population-based study of four United States communities. We used standardized protocols to assess photographs for the presence of retinal microvascular signs (retinopathy, arterio-venous nicking, and focal arteriolar narrowing) and a computer-assisted method to measure retinal vessel diameters. We analyzed DNA extracted from blood samples of participants for common allelic variants of the APOE gene.

RESULTS: After adjusting for age, gender, systolic blood pressure, smoking, total serum cholesterol, and other risk factors, we found white participants carrying the epsilon2 and epsilon4 alleles were more likely to have arterio-venous nicking than the epsilon3/epsilon3 homozygotes, with odds ratio (OR) of 1.70 and confidence interval (CI) 95\% (1.03-2.83) for the epsilon2 carriers and OR 1.74 (95\% CI 1.06-2.84) for the epsilon4 carriers. Among white participants without hypertension, the associations remained significant for the epsilon4 carriers (OR 2.32, 95\% CI 1.18-4.57). Whites, normotensive carriers of the epsilon2 allele had significantly narrower retinal arteriolar diameters (adjusted mean arteriolar diameter of 163.5 mum, 95\% CI 160.1-167.0, p=0.03) compared to the epsilon3/epsilon3 homozygotes (167.8 mum, 95\% CI 166.0-169.6). APOE gene polymorphism was not associated with retinopathy, focal narrowing, or retinal venular diameters in white participants. There were insufficient numbers of African-Americans for separate multivariate analysis.

CONCLUSIONS: This study provides little evidence that the APOE gene polymorphism plays a significant role in the pathogenesis of retinal microvascular changes in the general population. In the older white population, APOE epsilon2 and epsilon4 allele carriers were more likely to have arterio-venous nicking. Other retinal signs, however, were not related to APOE gene polymorphism.

}, keywords = {Aged, Aged, 80 and over, Apolipoprotein E2, Apolipoprotein E4, Apolipoproteins E, European Continental Ancestry Group, Female, Gene Frequency, Genotype, Heterozygote, Homozygote, Humans, Male, Microcirculation, Polymorphism, Genetic, Retinal Diseases, Retinal Vessels}, issn = {1090-0535}, author = {Sun, Cong and Tikellis, Gabriella and Liew, Gerald and Klein, Ronald and Larsen, Emily K Marino and Wong, Tien Y} } @article {6072, title = {Genome-wide association study of retinopathy in individuals without diabetes.}, journal = {PLoS One}, volume = {8}, year = {2013}, month = {2013}, pages = {e54232}, abstract = {

BACKGROUND: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.

METHODS: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.

RESULTS: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3{\textpm}0.23 (beta {\textpm} standard error), pā€Š=ā€Š6.6{\texttimes}10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (\~{}2\%), the quality of the imputation was moderate (r(2) \~{}0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.

CONCLUSIONS: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

}, keywords = {Aged, Aged, 80 and over, Female, Genome-Wide Association Study, Genotype, Histone Deacetylases, Humans, Hypertension, Male, Polymorphism, Single Nucleotide, Repressor Proteins, Retinal Diseases}, issn = {1932-6203}, doi = {10.1371/journal.pone.0054232}, author = {Jensen, Richard A and Sim, Xueling and Li, Xiaohui and Cotch, Mary Frances and Ikram, M Kamran and Holliday, Elizabeth G and Eiriksdottir, Gudny and Harris, Tamara B and Jonasson, Fridbert and Klein, Barbara E K and Launer, Lenore J and Smith, Albert Vernon and Boerwinkle, Eric and Cheung, Ning and Hewitt, Alex W and Liew, Gerald and Mitchell, Paul and Wang, Jie Jin and Attia, John and Scott, Rodney and Glazer, Nicole L and Lumley, Thomas and McKnight, Barbara and Psaty, Bruce M and Taylor, Kent and Hofman, Albert and de Jong, Paulus T V M and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Tay, Wan-Ting and Teo, Yik Ying and Seielstad, Mark and Liu, Jianjun and Cheng, Ching-Yu and Saw, Seang-Mei and Aung, Tin and Ganesh, Santhi K and O{\textquoteright}Donnell, Christopher J and Nalls, Mike A and Wiggins, Kerri L and Kuo, Jane Z and van Duijn, Cornelia M and Gudnason, Vilmundur and Klein, Ronald and Siscovick, David S and Rotter, Jerome I and Tai, E Shong and Vingerling, Johannes and Wong, Tien Y} }