Dataset Information

Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.

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.

SUBMITTER: Reynolds R

PROVIDER: S-EPMC3081670 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.

Reynolds Robyn R Rosner Bernard B Seddon Johanna M JM

Ophthalmology 20101001 10

<h4>Objective</h4>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.<h4>Design</h4>Case-control study.<h4>Participants</h4>A total of 458 participants from the Progression Study ...[more]

PMID: 20888482

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Project description:ObjectiveAge-related macular degeneration (AMD) is a significant cause of blindness, initially characterized by the accumulation of sub-Retinal pigment epithelium (RPE) deposits, leading to progressive retinal degeneration and, eventually, irreversible vision loss. This study aimed to elucidate the differential expression of transcriptomic information in AMD and normal human RPE choroidal donor eyes and to investigate whether it could be used as a biomarker for AMD.MethodsRPE choroidal tissue samples (46 Normal samples, 38 AMD samples) were obtained from the GEO (GSE29801) database and screened for differentially expressed genes in normal and AMD patients using GEO2R and R to compare the degree of enrichment of differentially expressed genes in the GO, KEGG pathway. Firstly, we used machine learning models (LASSO, SVM algorithm) to screen disease signature genes and compare the differences between these signature genes in GSVA and immune cell infiltration. Secondly, we also performed a cluster analysis to classify AMD patients. We selected the best classification by weighted gene co-expression network analysis (WGCNA) to screen the key modules and modular genes with the strongest association with AMD. Based on the module genes, four machine models, RF, SVM, XGB, and GLM, were constructed to screen the predictive genes and further construct the AMD clinical prediction model. The accuracy of the column line graphs was evaluated using decision and calibration curves.ResultsFirstly, we identified 15 disease signature genes by lasso and SVM algorithms, which were associated with abnormal glucose metabolism and immune cell infiltration. Secondly, we identified 52 modular signature genes by WGCNA analysis. We found that SVM was the optimal machine learning model for AMD and constructed a clinical prediction model for AMD consisting of 5 predictive genes.ConclusionWe constructed a disease signature genome model and an AMD clinical prediction model by LASSO, WGCNA, and four machine models. The disease signature genes are of great reference significance for AMD etiology research. At the same time, the AMD clinical prediction model provides a reference for early clinical detection of AMD and even becomes a future census tool. In conclusion, our discovery of disease signature genes and AMD clinical prediction models may become promising new targets for the targeted treatment of AMD.

Project description:PurposeTo characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS).DesignCross-sectional observational study.ParticipantsWe prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease.MethodsAll participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst.Main outcome measuresThe primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages.ResultsWe included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10-9) among these metabolites.ConclusionsParticipants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest that the most significant metabolites map to the glycerophospholipid pathway. These findings have the potential to improve our understanding of AMD pathogenesis, to support the development of plasma-based metabolomics biomarkers of AMD, and to identify novel targets for treatment of this blinding disease.

Dataset Information

Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.

Objective

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Publications

Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.

Similar Datasets

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