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Increased high-density lipoprotein levels associated with age-related macular degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia

Increased high-density lipoprotein levels associated with age-related macular degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia
Increased high-density lipoprotein levels associated with age-related macular degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia

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.

0161-6420
393-406
Colijn, Johanna M.
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Verzijden, Timo
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Meester-Smoor, Magda A.
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Klaver, Caroline C.W.
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Klaver, Caroline C.W.
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Lotery, Andrew
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European Eye Epidemiology Consortium
EYE-RISK Consortium
Colijn, Johanna M.
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Verzijden, Timo
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Meester-Smoor, Magda A.
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Klaver, Caroline C.W.
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Colijn, Johanna M.
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Demirkan, Ayse
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Verzijden, Timo
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Meester-Smoor, Magda A.
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Ahmad, Shahzad
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van Duijn, Cornelia M.
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Klaver, Caroline C.W.
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den Hollander, Anneke I.
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Kersten, Eveline
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Hoyng, Carel B.
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Klaver, Caroline C.W.
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Merle, Benedicte M.J.
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Korobelnik, Jean Francois
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Benlian, Pascale
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Bertelsen, Geir
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Bertelsen, Geir
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Bron, Alain M.
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Creuzot-Garcher, Catherine
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Claes, Birte
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Hense, Hans Werner
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Erke, Maja Gran
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Fauser, Sascha
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Khawaja, Anthony P.
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Hammond, Christopher J.
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Williams, Katie M.
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Piermarocchi, Stefano
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Segato, Tatiana
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Silva, Rufino
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Silva, Rufino
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Souied, Eric H.
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Papageorgiou, Grigorios
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Cree, Angela
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Lotery, Andrew
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European Eye Epidemiology Consortium and EYE-RISK Consortium (2019) Increased high-density lipoprotein levels associated with age-related macular degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia. Ophthalmology, 126 (3), 393-406. (doi:10.1016/j.ophtha.2018.09.045).

Record type: Article

Abstract

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.

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More information

Accepted/In Press date: 11 September 2018
e-pub ahead of print date: 10 October 2018
Published date: 1 March 2019

Identifiers

Local EPrints ID: 438700
URI: http://eprints.soton.ac.uk/id/eprint/438700
ISSN: 0161-6420
PURE UUID: 418bb1f8-a4b4-4e31-bddb-4eab3710ac26
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 23 Mar 2020 17:30
Last modified: 26 Nov 2021 02:47

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Contributors

Author: Johanna M. Colijn
Author: Timo Verzijden
Author: Magda A. Meester-Smoor
Author: Caroline C.W. Klaver
Author: Johanna M. Colijn
Author: Ayse Demirkan
Author: Timo Verzijden
Author: Magda A. Meester-Smoor
Author: Shahzad Ahmad
Author: Cornelia M. van Duijn
Author: Caroline C.W. Klaver
Author: Anneke I. den Hollander
Author: Eveline Kersten
Author: Carel B. Hoyng
Author: Caroline C.W. Klaver
Author: Audrey Cougnard-Grégoire
Author: Benedicte M.J. Merle
Author: Jean Francois Korobelnik
Author: Cécile Delcourt
Author: Grigorios Papageorgiou
Author: Monique T. Mulder
Author: Miguel Angelo Costa
Author: Rufino Silva
Author: Pascale Benlian
Author: Geir Bertelsen
Author: Geir Bertelsen
Author: Alain M. Bron
Author: Catherine Creuzot-Garcher
Author: Birte Claes
Author: Hans Werner Hense
Author: Maja Gran Erke
Author: Sascha Fauser
Author: Sascha Fauser
Author: Paul J. Foster
Author: Anthony P. Khawaja
Author: Paul J. Foster
Author: Christopher J. Hammond
Author: Katie M. Williams
Author: Christopher J. Hammond
Author: Katie M. Williams
Author: Anthony P. Khawaja
Author: Jean Francois Korobelnik
Author: Stefano Piermarocchi
Author: Tatiana Segato
Author: Rufino Silva
Author: Rufino Silva
Author: Eric H. Souied
Author: Grigorios Papageorgiou
Author: Angela Cree
Author: Andrew Lotery ORCID iD
Corporate Author: European Eye Epidemiology Consortium
Corporate Author: EYE-RISK Consortium

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