TY - JOUR
T1 - Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia
AU - Colijn, Johanna M.
AU - Verzijden, Timo
AU - Meester-Smoor, Magda A.
AU - Klaver, Caroline C.W.
AU - Colijn, Johanna M.
AU - Demirkan, Ayse
AU - Verzijden, Timo
AU - Meester-Smoor, Magda A.
AU - Ahmad, Shahzad
AU - van Duijn, Cornelia M.
AU - den Hollander, Anneke I.
AU - Kersten, Eveline
AU - Hoyng, Carel B.
AU - Klaver, Caroline C.W.
AU - EYE-RISK consortium
AU - European Eye Epidemiology Consortium
AU - Cougnard-Grégoire, Audrey
AU - Merle, Benedicte M.J.
AU - Korobelnik, Jean Francois
AU - Delcourt, Cécile
AU - Papageorgiou, Grigorios
AU - Mulder, Monique T.
AU - Costa, Miguel Angelo
AU - Silva, Rufino
AU - Benlian, Pascale
AU - Bertelsen, Geir
AU - Bertelsen, Geir
AU - Bron, Alain M.
AU - Creuzot-Garcher, Catherine
AU - Claes, Birte
AU - Hense, Hans Werner
AU - Erke, Maja Gran
AU - Fauser, Sascha
AU - Fauser, Sascha
AU - Foster, Paul J.
AU - Khawaja, Anthony P.
AU - Foster, Paul J.
AU - Hammond, Christopher J.
AU - Williams, Katie M.
AU - Hammond, Christopher J.
AU - Williams, Katie M.
AU - Khawaja, Anthony P.
AU - Korobelnik, Jean François
AU - Azuara-Blanco, Augusto
AU - Chakravarthy, Usha
AU - Hogg, Ruth
AU - Muldrew, Alyson
AU - Peto, Tunde
AU - Silvestri, Giuliana
AU - Lengyel, Imre
AU - Peto, Tunde
PY - 2019/3/1
Y1 - 2019/3/1
N2 -
Purpose: Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design: Pooled analysis of cross-sectional data. Participants: Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods: AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures: AMD features and stage; lipid measurements. Results: HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10
–7
), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10
–6
and P = 1.6 × 10
–4
). Conclusions: Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.
AB -
Purpose: Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design: Pooled analysis of cross-sectional data. Participants: Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods: AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures: AMD features and stage; lipid measurements. Results: HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10
–7
), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10
–6
and P = 1.6 × 10
–4
). Conclusions: Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.
U2 - 10.1016/j.ophtha.2018.09.045
DO - 10.1016/j.ophtha.2018.09.045
M3 - Article
C2 - 30315903
AN - SCOPUS:85057508316
SN - 0161-6420
VL - 126
SP - 393
EP - 406
JO - Ophthalmology
JF - Ophthalmology
IS - 3
ER -