TY - JOUR
T1 - Copy number variations in candidate genes in neovascular age-related macular degeneration
AU - Liu, Melissa M.
AU - Agrón, Elvira
AU - Chew, Emily
AU - Meyerle, Catherine
AU - Ferris, Frederick L.
AU - Chan, Chi Chao
AU - Tuo, Jingsheng
PY - 2011/5
Y1 - 2011/5
N2 - Purpose. The pathogenesis of age-related macular degeneration (AMD) is strongly influenced by genetic factors, and single nucleotide polymorphisms have been consistently linked to AMD. Copy number variation (CNV), or variation in the number of copies of a particular segment of DNA, may also contribute to AMD pathogenesis. This study evaluated CNVs in candidate genes that have been reported to be linked to AMD. Methods. Study participants were 131 patients with neovascular AMD and 103 elderly persons without AMD who were evaluated by retinal specialists at the National Eye Institute. DNA was collected from peripheral whole blood, and duplex RT-PCR based copy number (CN) assays were performed for the genes CCR3, CFH, CX3CR1, ERCC6, HTRA1, and VEGF. Quantitative CNs (CN = 0, 1, 2, or 3+) were determined. Results. Novel CNVs were discovered in CCR3, CX3CR1, and ERCC6. The unadjusted data suggested that CN = 3+ for CX3CR1 might be mildly protective against AMD, but this trend did not persist after adjustment for age. AMD patients appeared to have an elevated mean CFH CN relative to controls (2.13 [95% confidence interval (CI), 2.05-2.21] vs. 2.01 [95% CI, 1.92-2.09 copies]; P = 0.05). No significant associations between CNV and AMD were observed for the remaining genes. Conclusions. The methods described are suitable for quantitative characterization of CNV in candidate genes. The authors identified CNVs in AMD-associated genes but did not find strong evidence for a link with neovascular AMD.
AB - Purpose. The pathogenesis of age-related macular degeneration (AMD) is strongly influenced by genetic factors, and single nucleotide polymorphisms have been consistently linked to AMD. Copy number variation (CNV), or variation in the number of copies of a particular segment of DNA, may also contribute to AMD pathogenesis. This study evaluated CNVs in candidate genes that have been reported to be linked to AMD. Methods. Study participants were 131 patients with neovascular AMD and 103 elderly persons without AMD who were evaluated by retinal specialists at the National Eye Institute. DNA was collected from peripheral whole blood, and duplex RT-PCR based copy number (CN) assays were performed for the genes CCR3, CFH, CX3CR1, ERCC6, HTRA1, and VEGF. Quantitative CNs (CN = 0, 1, 2, or 3+) were determined. Results. Novel CNVs were discovered in CCR3, CX3CR1, and ERCC6. The unadjusted data suggested that CN = 3+ for CX3CR1 might be mildly protective against AMD, but this trend did not persist after adjustment for age. AMD patients appeared to have an elevated mean CFH CN relative to controls (2.13 [95% confidence interval (CI), 2.05-2.21] vs. 2.01 [95% CI, 1.92-2.09 copies]; P = 0.05). No significant associations between CNV and AMD were observed for the remaining genes. Conclusions. The methods described are suitable for quantitative characterization of CNV in candidate genes. The authors identified CNVs in AMD-associated genes but did not find strong evidence for a link with neovascular AMD.
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U2 - 10.1167/iovs.10-6735
DO - 10.1167/iovs.10-6735
M3 - Article
C2 - 21273533
AN - SCOPUS:79960942836
SN - 0146-0404
VL - 52
SP - 3129
EP - 3135
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 6
ER -