Dataset Information

Gout and the risk of age-related macular degeneration in the elderly.

ABSTRACT:

Objective

To assess whether gout is associated with incident age-related macular degeneration (AMD).

Methods

We used the 5% Medicare claims data from 2006-12 for all beneficiaries who were enrolled in Medicare fee-for-service (Parts A, B) and not enrolled in a Medicare Advantage Plan, and resided in the U.S. People were censored at the occurrence of new diagnosis of AMD, death or the end of study (12/31/2012), whichever occurred first. We used multivariable-adjusted Cox regression analyses to assess the association of gout with incident AMD, adjusted for demographics, comorbidity, and use of medications for cardiovascular disease and gout. Hazard ratios and 95% confidence intervals were calculated.

Results

In this observational cohort study, of the 1,684,314 eligible people, 116,097 developed incident AMD (6.9%). Incidence rates of AMD per 1,000 person-years were 20.1 for people with gout and 11.7 for people without gout. In multivariable-adjusted analyses, a diagnosis of gout was significantly associated with a higher risk of incident AMD with a hazard ratio of 1.39 (95% CI, 1.35, 1.43). This association was confirmed in sensitivity analyses that substituted Charlson-Romano comorbidity index continuous score with either a categorical Charlson-Romano comorbidity index score or individual Charlson-Romano index comorbidities plus hypertension, hyperlipidemia and coronary artery disease. Other covariates significantly associated with higher hazards of incident AMD were older age, female gender, White race/ethnicity, and higher Charlson-Romano comorbidity index score.

Conclusions

We noted a novel association of gout with AMD in the elderly. Future studies should investigate the pathways that mediate this association.

SUBMITTER: Singh JA

PROVIDER: S-EPMC6042699 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Gout and the risk of age-related macular degeneration in the elderly.

Singh Jasvinder A JA Cleveland John D JD

PloS one 20180712 7

<h4>Objective</h4>To assess whether gout is associated with incident age-related macular degeneration (AMD).<h4>Methods</h4>We used the 5% Medicare claims data from 2006-12 for all beneficiaries who were enrolled in Medicare fee-for-service (Parts A, B) and not enrolled in a Medicare Advantage Plan, and resided in the U.S. People were censored at the occurrence of new diagnosis of AMD, death or the end of study (12/31/2012), whichever occurred first. We used multivariable-adjusted Cox regression ...[more]

PMID: 30001351

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Project description:PURPOSE:Age-related macular degeneration (AMD) is a degenerative disease of the macula, often leading to progressive vision loss. The rate of disease progression can vary among individuals and has been associated with multiple risk factors. In this review, we provide an overview of the current literature investigating phenotypic, demographic, environmental, genetic, and molecular risk factors, and propose the most consistently identified risk factors for disease progression in AMD based on these studies. Finally, we describe the potential use of these risk factors for personalised healthcare. RECENT FINDINGS:While phenotypic risk factors such as drusen and pigment abnormalities become more important to predict disease progression during the course of the disease, demographic, environmental, genetic and molecular risk factors are more valuable at earlier disease stages. Demographic and environmental risk factors such as age and smoking are consistently reported to be related to disease progression, while other factors such as sex, body mass index (BMI) and education are less often associated. Of all known AMD variants, variants that are most consistently reported with disease progression are rs10922109 and rs570618 in CFH, rs116503776 in C2/CFB/SKIV2L, rs3750846 in ARMS2/HTRA1 and rs2230199 in C3. However, it seems likely that other AMD variants also contribute to disease progression but to a lesser extent. Rare variants have probably a large effect on disease progression in highly affected families. Furthermore, current prediction models do not include molecular risk factors, while these factors can be measured accurately in the blood. Possible promising molecular risk factors are High-Density Lipoprotein Cholesterol (HDL-C), Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), zeaxanthin and lutein. SUMMARY:Phenotypic, demographic, environmental, genetic and molecular risk factors can be combined in prediction models to predict disease progression, but the selection of the proper risk factors for personalised risk prediction will differ among individuals and is dependent on their current disease stage. Future prediction models should include a wider set of genetic variants to determine the genetic risk more accurately, and rare variants should be taken into account in highly affected families. In addition, adding molecular factors in prediction models may lead to preventive strategies and personalised advice.

Project description:PurposeTo determine the contribution of common and rare genetic risk variants in families with age-related macular degeneration (AMD).DesignCase-control study.ParticipantsA family cohort (355 affected and 342 unaffected family members from 144 families with AMD) and an unrelated case-control cohort (1078 patients, 952 controls), recruited from the European Genetic Database.MethodsGenetic data of both cohorts were filtered for carriership of rare genetic variants in the coding and splice-site regions of the complement factor H (CFH) and complement factor I (CFI) genes, and 52 AMD-associated variants were extracted for calculation of genetic risk scores (GRS). To compare GRSs between familial and nonfamilial rare CFH and CFI variant carriers and noncarriers and between AMD disease stages, we performed a 2-way analysis of variance, with Bonferroni correction for multiple testing. Within families with AMD carrying rare CFH and CFI variants, we analyzed segregation patterns by calculating the proportion of affected among carriers.Main outcome measuresGRSs and segregation of rare CFH and CFI variants.ResultsWe observed higher GRSs in familial versus nonfamilial individuals without rare CFH and CFI variants: mean GRS, 1.76 (standard error [SE], 0.08) versus 0.83 (SE, 0.03; P < 0.001). In 51 of 144 families (35.4%), rare CFH and CFI variants were identified. Within the AMD family cohort, carriers of rare CFH and CFI variants showed lower GRSs compared with noncarriers (mean GRS, 1.05 [SE, 0.23] vs. 1.76 [SE, 0.08]; P = 0.02). The proportion of affected family members with a high GRS was 57.3% (176/307). Of the affected family members with a low or intermediate GRS, 40.0% carried rare CFH or CFI variants. Among carriers of 11 rare CFH or CFI variants, the proportion affected by AMD was more than 75%.ConclusionsGenetic risk in families with AMD often is attributed to high GRSs based on common variants. However, in part of the families with a low or intermediate GRS, rare CFH and CFI variants contributed to disease development. We recommend computing GRSs and sequencing the CFH and CFI genes in families with AMD, in particular in the light of ongoing gene-specific clinical trials.

Dataset Information

Gout and the risk of age-related macular degeneration in the elderly.

Objective

Methods

Results

Conclusions

Publications

Gout and the risk of age-related macular degeneration in the elderly.

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