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Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.
MedLine Citation:
PMID:  20888482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: A genetic variant in the high-density lipoprotein (HDL) cholesterol pathway, hepatic lipase (LIPC), was discovered to be associated with advanced age-related macular degeneration (AMD) in a genome-wide association study. In this study, we evaluated whether LIPC is associated with serum lipids, and whether this gene and serum lipids are independently associated with AMD.
DESIGN: Case-control study.
PARTICIPANTS: A total of 458 participants from the Progression Study of Macular Degeneration and the Age-Related Eye Disease Ancillary Biomarker Study, including 318 advanced AMD cases with either geographic atrophy (n = 123) or neovascular disease (n = 195) and 140 controls.
METHODS: Participants were genotyped for 8 variants associated with AMD: 2 CFH variants, C2, CFB, C3, CFI, the ARMS2/HTRA1 gene region, and LIPC. Fasting blood specimens were obtained at study onset, and serum levels of total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides were determined. Logistic and linear regression were used to evaluate associations between serum lipids, LIPC genotype, and AMD.
MAIN OUTCOME MEASURES: LIPC and serum lipid associations with AMD.
RESULTS: The minor T allele of the LIPC gene was associated with a reduced risk of AMD (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P = 0.01, trend for number of T alleles, controlling for age and gender). Mean level of HDL was lower (P = 0.05) and mean level of LDL (P = 0.03) was higher in cases of advanced AMD compared with controls. Higher total cholesterol and LDL levels were associated with increased risk of AMD, with P for trend = 0.01 for both, in models controlling for environmental and genetic covariates. The T allele of LIPC was associated with higher levels of HDL, although LIPC was associated with advanced AMD independent of HDL level.
CONCLUSIONS: The HDL-raising allele of the LIPC gene (T) was associated with a reduced risk of AMD. Higher total cholesterol and LDL levels were associated with increased risk, whereas higher HDL levels tended to reduce the risk of AMD. The specific mechanisms underlying the association between AMD and LIPC require further investigation.
Authors:
Robyn Reynolds; Bernard Rosner; Johanna M Seddon
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Ophthalmology     Volume:  117     ISSN:  1549-4713     ISO Abbreviation:  Ophthalmology     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-20     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  7802443     Medline TA:  Ophthalmology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1989-95     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Affiliation:
Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts 02111, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Biological Markers / blood*
Case-Control Studies
Cholesterol, HDL / blood*
Cholesterol, LDL / blood
Female
Genetic Markers
Genotype
Humans
Lipase / genetics*
Macular Degeneration / blood*,  genetics*
Male
Risk Factors
Triglycerides / blood
Grant Support
ID/Acronym/Agency:
R01 EY011309-14/EY/NEI NIH HHS; R01 EY011309-15/EY/NEI NIH HHS; R01-EY11309/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Genetic Markers; 0/Triglycerides; EC 3.1.1.3/LIPH protein, human; EC 3.1.1.3/Lipase
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