Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium

Ronald Klein; Chelsea E Myers; Gabriëlle H S Buitendijk; Elena Rochtchina; Xiaoyi Gao; Paulus T V M de Jong; Theru A Sivakumaran; George Burlutsky; Roberta McKean-Cowdin; Albert Hofman; Sudha K Iyengar; Kristine E Lee; Bruno H Stricker; Johannes R Vingerling; Paul Mitchell; Barbara E K Klein; Caroline C W Klaver; Jie Jin Wang

doi:10.1016/j.ajo.2014.05.027

Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium

Am J Ophthalmol. 2014 Sep;158(3):513-24.e3. doi: 10.1016/j.ajo.2014.05.027. Epub 2014 May 28.

Authors

Ronald Klein¹, Chelsea E Myers², Gabriëlle H S Buitendijk³, Elena Rochtchina⁴, Xiaoyi Gao⁵, Paulus T V M de Jong⁶, Theru A Sivakumaran⁷, George Burlutsky⁴, Roberta McKean-Cowdin⁸, Albert Hofman⁹, Sudha K Iyengar¹⁰, Kristine E Lee², Bruno H Stricker¹¹, Johannes R Vingerling³, Paul Mitchell¹², Barbara E K Klein², Caroline C W Klaver³, Jie Jin Wang¹³

Affiliations

¹ Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address: kleinr@epi.ophth.wisc.edu.
² Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
³ Department of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
⁴ Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia; Clinical Ophthalmology & Eye Health, University of Sydney, Westmead, New South Wales, Australia.
⁵ Keck School of Medicine, University of Southern California, Los Angeles, California.
⁶ Netherlands Institute of Neurosciences, Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands; Department of Ophthalmology, Academic Medical Center, Amsterdam, Netherlands; Department of Ophthalmology, Leiden University Medical Center, Leiden, Netherlands.
⁷ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
⁸ Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Preventive Medicine, University of Southern California, Los Angeles, California.
⁹ Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, the Hague, Netherlands.
¹⁰ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
¹¹ Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
¹² Clinical Ophthalmology & Eye Health, University of Sydney, Westmead, New South Wales, Australia.
¹³ Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.

Abstract

Purpose: To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD).

Design: Meta-analysis.

Methods: setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD.

Results: The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis.

Conclusion: In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Disease Progression
Global Health
Humans
Incidence
Lipid Metabolism / genetics*
Lipids / physiology*
Macular Degeneration* / epidemiology
Macular Degeneration* / genetics
Macular Degeneration* / metabolism
Risk Factors

Substances

Lipids

Abstract

Publication types

MeSH terms

Substances

Grants and funding