TY - JOUR
T1 - Genetic association of apolipoprotein E with age-related macular degeneration
AU - Klaver, Caroline C.W.
AU - Kliffen, Mike
AU - Van Duijn, Cornelia M.
AU - Hofman, Albert
AU - Cruts, Marc
AU - Grobbee, Diederick E.
AU - Van Broeckhoven, Christine
AU - De Jong, Paulus T.V.M.
PY - 1998/1/1
Y1 - 1998/1/1
N2 - Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic- association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE ε4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0.88]), and the ε2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2.82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.
AB - Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic- association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE ε4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0.88]), and the ε2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2.82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.
UR - http://www.scopus.com/inward/record.url?scp=0032231956&partnerID=8YFLogxK
U2 - 10.1086/301901
DO - 10.1086/301901
M3 - Article
C2 - 9634502
AN - SCOPUS:0032231956
SN - 0002-9297
VL - 63
SP - 200
EP - 206
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -