Dataset Information

Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study.

ABSTRACT: To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study.1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression.Twenty-one SNPs from 11 genes were associated with MPOD (P ? 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (?A = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)).Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.

SUBMITTER: Meyers KJ

PROVIDER: S-EPMC3626525 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study.

Meyers Kristin J KJ Johnson Elizabeth J EJ Bernstein Paul S PS Iyengar Sudha K SK Engelman Corinne D CD Karki Chitra K CK Liu Zhe Z Igo Robert P RP Truitt Barbara B Klein Michael L ML Snodderly D Max DM Blodi Barbara A BA Gehrs Karen M KM Sarto Gloria E GE Wallace Robert B RB Robinson Jennifer J LeBlanc Erin S ES Hageman Gregory G Tinker Lesley L Mares Julie A JA

Investigative ophthalmology & visual science 20130328 3

<h4>Purpose</h4>To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study.<h4>Methods</h4>1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes rela ...[more]

PMID: 23404124

Similar Datasets

Project description:PurposeTo report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy.DesignProspective cohort within a randomized, controlled trial of oral micronutrient supplements.ParticipantsAge-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy.MethodsColor fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression.Main outcome measuresIncident macular atrophy after nAMD.ResultsOf the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3.ConclusionsThe rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Project description:PurposeTo determine the prevalence of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD), assess the role of RPD as an independent risk factor for late AMD development, and evaluate genetic association with RPD.DesignProspective cohort study.ParticipantsParticipants with intermediate AMD in 1 or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplement.MethodsFundus autofluorescence (FAF) images from a subset of AREDS2 participants were evaluated at annual visits for presence of RPD. Six single nucleotide polymorphisms-rs10490924 (ARMS2), rs1061170 (CFH), rs2230199 (C3), rs116503776 and rs114254831 (C2/CFB), and rs943080 (VEGF-A)-and the genetic risk score (GRS) were assessed for association with RPD. Development of late AMD, defined as geographic atrophy (GA) or neovascular AMD (NVAMD), was identified.Main outcome measuresPrevalence of RPD, odds ratio (OR) of late AMD development, and genetic associations of RPD.ResultsThe FAF images were evaluated for 5021 eyes (2516 participants). Reticular pseudodrusen were seen in 1186 eyes (24% of eyes, 29% of participants). Prevalence of RPD varied with baseline AREDS AMD severity level: 6% in early AMD (n = 458), 26% in intermediate AMD (n = 2606), 36% in GA (n = 682), and 19% in NVAMD (n = 1246). Mean age of participants with RPD was 79 years (standard deviation [SD], 7) and 75 years (SD, 8) in those without RPD (P < 0.0001). Reticular pseudodrusen were more frequent in female participants (65% RPD vs. 53% no RPD). Odds ratio adjusted for baseline age, gender, race, educational status, smoking, and AMD severity level for 1710 eyes at risk of developing late AMD at the next annual visit was 2.42 (95% confidence interval [CI], 1.80-3.24; P < 0.001) for GA and 1.21 (95% CI, 0.87-1.7; P = 0.26) for NVAMD. Presence of RPD was significantly associated with higher GRS (P < 0.0001) and ARMS2 risk alleles (P < 0.0001) and, at a nominal level, with C3 risk alleles (P = 0.04) and CFH risk alleles (P = 0.048 for homozygotes).ConclusionsParticipants with RPD have an increased risk of progression to GA but not NVAMD. ARMS2 risk alleles and higher GRS were associated with the presence of RPD. This study suggests that RPD are an important risk marker and should be included in classification systems used for patient prognosis.

Project description:Purpose:To identify the development and progression of macular retinal pigment epithelial atrophy in eyes with neovascular (CNV) age-related macular degeneration (AMD) and to correlate with visual acuity (VA). Design:Cohort study. Participants:Age-Related Eye Disease Study 2 (AREDS2) participants with intermediate AMD enrolled in a randomized controlled clinical trial of oral supplements. Analyses were conducted in the subset of AREDS2 participants who were also enrolled in the fundus autofluorescence ancillary (FAF) ancillary study. Methods:Color photographs and FAF images were evaluated in eyes that developed CNV. Presence of geographic atrophy (GA) prior to the incidence of CNV and the development of macular atrophy following incident CNV were assessed. Areas of hypoautofluorescence representing atrophy were measured for area and macular involvement. Enlargement rate of atrophy and change in visual acuity over time were analyzed. Main Outcome Measures:incidence and enlargement rate of atrophy and VA changes in eyes with incident CNV. Results:Incident CNV developed in 334 (9.2%) of eyes evaluated in the AREDS2 FAF substudy. Of these, 40% had macular atrophy at incidence of CNV with half of these attributable to pre-existing GA. Atrophy developed in 14.7 % of eyes over 4 years of follow-up. Mean area of atrophy was largest in eyes with pre-existing GA and CNV (5.17 mm2, p<0.001), and atrophy involved the center of the macula in > 65% of eyes. Mean VA letter score at the annual visit in which CNV was documented was similar in the three groups with atrophy; eyes with CNV and pre-existing GA, incident atrophy at the first visit with CNV, and atrophy during follow up (60 letters). Enlargement rate of atrophy was also similar in eyes in the three groups (1.23 - 1.86 mm2, p = 0.47). Eyes with macular atrophy lost more visual acuity compared to eyes without atrophy, particularly after 2 years of follow-up (-10.9 vs. - 3.6 letters, p = 0.07). Conclusion:Atrophy is commonly seen in neovascular AMD and often can be attributed to pre-existing GA. Macular atrophy and GA appear to be a continuum of the same disease process and are both associated with poor vision.

Project description:Importance:Previous studies of the role of dietary and supplementary calcium in age-related macular degeneration (AMD) have produced mixed results, suggesting that supplementation and decreased dietary intake are both harmful. Objective:To evaluate the association of baseline dietary and supplementary calcium intake with progression of AMD. Design, Setting, and Participants:This study involved secondary analyses of participants enrolled in the Age-Related Eye Disease Study (AREDS). The AREDS study (1992-2001) enrolled patients from academic and community-based retinal practices in the United States. Men and women with varying severity of AMD were included. Data analysis for this article occurred from September 2015 to December 2018. Exposures:Baseline self-reported dietary or supplementary calcium intake. Main Outcomes and Measures:Development of late AMD, geographic atrophy (central or noncentral), or neovascular AMD detected on centrally graded baseline and annual fundus photographs. Results:A total of 4751 participants were included (mean [SD] age, 69.4 [5.1] years); 4543 (95.6%) were white, and 2655 (55.9%) were female. Compared with those who were in the lowest quintile, the participants in the highest quintile of dietary calcium intake had a lower risk of developing late AMD (hazard ratio [HR], 0.73 [95% CI, 0.59-0.90]), central geographic atrophy (HR, 0.64 [95% CI, 0.48-0.86]), and any geographic atrophy (HR, 0.80 [95% CI, 0.64-1.00]). The participants in the highest tertile of supplementary calcium intake had a lower risk of developing neovascular AMD (HR, 0.70 [95% CI, 0.50-0.97]) compared with those who did not take calcium supplements. When stratified by sex, women in the highest quintile of dietary calcium intake had a lower risk of developing late AMD (HR, 0.73 [95% CI, 0.56-0.97]) compared with those in the lowest quintile. Women in the highest tertile of calcium supplementation had a lower risk of progression to neovascular AMD (HR, 0.67 [95% CI, 0.48-0.94]) compared with those who did not take calcium supplements. Similar findings were found in men for dietary calcium. Too few men took calcium supplements to allow for analyses. Conclusions and Relevance:In this secondary analysis, higher levels of dietary and supplementary calcium intake were associated with lower incidence of progression to late AMD in AREDS participants. The results may be owing to uncontrolled confounding or chance and should be considered hypothesis development requiring additional study.

Dataset Information

Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study.

Publications

Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets