Robyn Reynolds1, Bernard Rosner, Johanna M Seddon. 1. Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts 02111, USA.
Abstract
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.
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: Redmer van Leeuwen; M Kamran Ikram; Johannes R Vingerling; Jacqueline C M Witteman; Albert Hofman; Paulus T V M de Jong Journal: Invest Ophthalmol Vis Sci Date: 2003-09 Impact factor: 4.799
Authors: Redmer van Leeuwen; Caroline C W Klaver; Johannes R Vingerling; Albert Hofman; Cornelia M van Duijn; Bruno H Ch Stricker; Paulus T V M de Jong Journal: Am J Ophthalmol Date: 2004-04 Impact factor: 5.258
Authors: Sandra C Tomany; Jie Jin Wang; Redmer Van Leeuwen; Ronald Klein; Paul Mitchell; Johannes R Vingerling; Barbara E K Klein; Wayne Smith; Paulus T V M De Jong Journal: Ophthalmology Date: 2004-07 Impact factor: 12.079
Authors: Yi Yu; Robyn Reynolds; Jesen Fagerness; Bernard Rosner; Mark J Daly; Johanna M Seddon Journal: Invest Ophthalmol Vis Sci Date: 2011-06-28 Impact factor: 4.799
Authors: Nicole A Restrepo; Kylee L Spencer; Robert Goodloe; Tiana A Garrett; Gerardo Heiss; Petra Bůžková; Neal Jorgensen; Richard A Jensen; Tara C Matise; Lucia A Hindorff; Barbara E K Klein; Ronald Klein; Tien Y Wong; Ching-Yu Cheng; Belinda K Cornes; E-Shyong Tai; Marylyn D Ritchie; Jonathan L Haines; Dana C Crawford Journal: Invest Ophthalmol Vis Sci Date: 2014-09-09 Impact factor: 4.799
Authors: Nathan G Lambert; Hanan ElShelmani; Malkit K Singh; Fiona C Mansergh; Michael A Wride; Maximilian Padilla; David Keegan; Ruth E Hogg; Balamurali K Ambati Journal: Prog Retin Eye Res Date: 2016-05-06 Impact factor: 21.198