Genetic association study of age-related macular degeneration in the Spanish population

Brión, Marı́a; Sánchez-Salorio, Manuel; Cortón, Marta; Fuente, María de la; Pazos, Belen; Othman, Mohammad; Swaroop, Anand; Abecasis, Gonçalo R.; Sobrino, Beatriz; Carracedo, Ángel

doi:10.1111/j.1755-3768.2010.02040.x

Cited by 35 publications

(27 citation statements)

References 69 publications

(102 reference statements)

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“…PON1 has an equally broad infl uence on human health, having been linked to vascular disease, Parkinson's disease ( 57-59 ), systemic lupus erythematosus ( 60-62 ), breast cancer ( 63, 64 ), age-related macular degeneration (65)(66)(67)(68)(69)(70)(71), and diabetes ( 36, 37 ) among other disorders. A fuller understanding of the determinants of PON1 activity should include the effects of diet.…”

Section: Discussionmentioning

confidence: 99%

Dietary cholesterol increases paraoxonase 1 enzyme activity

Kim

Burt

Ranchalis

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org High density lipoprotein (HDL) levels have long believed to be cardioprotective ( 1 ) through a variety of processes, including reverse cholesterol transport in which excess cholesterol is taken to the liver for excretion ( 2 ). However, recent studies have highlighted the need to better understand the cardioprotective role of HDL. For example, two recent Mendelian randomization studies found that single nucleotide polymorphisms (SNP) that predict plasma HDL cholesterol (HDL-C) variance were not associated with myocardial infarction (MI) ( 3, 4 ). Moreover, a recent drug trial with torcetrapib, a cholesterol ester transport protein inhibitor, found that although torcetrapib increased levels of HDL and lowered deleterious low density lipoprotein (LDL) levels, it did not affect atherosclerotic measures and paradoxically led to an increase in adverse cardiovascular events ( 5 ). In addition, a recent large randomized clinical trial did not show a benefi t of niacin in preventing adverse cardiovascular outcomes, despite improved levels of HDL-C and triglycerides in the treatment group ( 6 ). These results refocus attention on the many aspects of HDL biology that are not captured by serum measurements of HDL, such as its paraoxonase 1 (PON1) activity, which itself is inversely associated with cardiovascular and other human diseases.The activity of PON1 , a liver-produced glycoprotein enzyme bound to the surface of HDL, is consistently correlated with atherosclerotic vascular disease and end-organ damage ( 7-9 ). PON1 is at least partially responsible for the cardioprotective inhibitory effects of HDL on LDL peroxidation ( 10-12 ), and it also has been demonstrated to hydrolyze oxidized lipid or lipid hydroperoxides in LDL ( 13 ). Inactivation of PON1 reduced the ability of HDL to Abstract HDL-associated paraoxonase 1 (PON1) activity has been consistently associated with cardiovascular and other diseases. Vitamins C and E intake have previously been positively associated with PON1 in a subset of the Carotid Lesion Epidemiology and Risk (CLEAR) cohort. The goal of this study was to replicate these fi ndings and determine whether other nutrient intake affected PON1 activity. To predict nutrient and mineral intake values, 1,402 subjects completed a standardized food frequency survey of their dietary habits over the past year. Stepwise regression was used to evaluate dietary and covariate effects on PON1 arylesterase activity. Five dietary components, cholesterol ( P < 2.0 × 10 ؊ 16 ), alcohol ( P = 8.51 × 10 ؊ 8 ), vitamin C ( P = 7.97 × 10 ؊ 5 ), iron ( P = 0.0026), and folic acid (0.037) were independently predictive of PON1 activity. Dietary cholesterol was positively associated and predicted 5.5% of PON1 activity, second in variance explained. This study presents a novel fi nding of dietary cholesterol, iron, and folic acid predicting PON1 activity in humans and confi rms prior reported associations, including that with vitamin C. Identifying and understanding en...

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Section: Discussionmentioning

confidence: 99%

Dietary cholesterol increases paraoxonase 1 enzyme activity

Kim

Burt

Ranchalis

et al. 2012

Journal of Lipid Research

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“…ARMS2 gene polymorphism has been reported to be a significant AMD risk factor in the Spanish population (Brión et al, 2011). In addition, Cruz-González et al (2014) identified a significant association between rs10490923 and the risk of developing AMD among Spanish individuals.…”

Section: Discussionmentioning

confidence: 97%

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients

et al. 2017

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ABSTRACT. Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is a complex disease with both genetic and environmental risk factors. To improve clinical management of this condition, it is important to develop risk assessment and prevention strategies for environmental influences, and establish a more effective treatment approach. The aim of the present study was to investigate age-related maculopathy susceptibility protein 2 (ARMS2) gene sequences among Turkish patients with exudative AMD. In addition to 39 advanced exudative AMD patients, 250 healthy individuals for whom exome sequencing data were available were included as a control group. Patients with a history of known environmental and systemic AMD risk factors were excluded. Genomic DNA was isolated from peripheral blood and analyzed using next-generation sequencing. All coding exons of the ARMS2 gene were assessed. Three different ARMS2 sequence variations (rs10490923, rs2736911, and rs10490924) were identified in both the patient and control group. Within the control group, two further ARMS2 gene variants (rs7088128 and rs36213074) were also detected. Logistic regression analysis revealed a relationship between the rs10490924 polymorphism and AMD in the Turkish population.

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“…We are currently applying the evidence base presented in Table 2 and Figure 1 to guide investigations designed to identify core elements of a "molecular phenotype" (a pattern gene regulation/expression and DNA variation) representing individual capacity to use transporters, receptors, enzymes, and hormones targeting or affected by MXs in ways that may reduce risk of AMD incidence or progression. Although we have not yet identified any single sequence variant explaining a proportion of variance in AMD risk comparable to those of the complement pathway genes, there is now informative work examining putative AMD-associated single-nucleotide polymorphisms present in genes encoding proteins involved in MX transport (121,131,137,146,(148)(149)(150)(151)(152)(153)(154)(156)(157)(158)(159)(160)(161), binding/capture (141,162,163), cleavage (158,160), and diseases associated with lower MX status (177)(178)(179)(180)(181)(182)(183)(184). Projects examining the associations of MX-related genes with retinal pathophysiology in in vivo models have supported inferences on AMD relations with variants in MX transport genes (128,130,136,143).…”

Section: The Promise Of Molecular Genetics For Examining the Effect Omentioning

confidence: 98%

“…[177][178][179][180][181][182][183][184] Numbers in parentheses correspond to reference numbers. Full names for genes represented by symbols are available from http://www.ncbi.nlm.nih.gov/gene.…”

mentioning

confidence: 99%

The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field

SanGiovanni¹,

Neuringer²

2012

The American Journal of Clinical Nutrition

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Age-related macular degeneration (AMD) is the primary cause of vision loss in elderly people of western European ancestry. Genetic, dietary, and environmental factors affect tissue concentrations of macular xanthophylls (MXs) within retinal cell types manifesting AMD pathology. In this article we review the history and state of science on the putative role of the MXs (lutein, zeaxanthin, and meso-zeaxanthin) in AMD and report findings on AMD-associated genes encoding enzymes, transporters, ligands, and receptors affecting or affected by MXs. We then use this context to discuss emerging research opportunities that offer promise for meaningful investigation and inference in the field.

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Genetic association study of age-related macular degeneration in the Spanish population

Cited by 35 publications

References 69 publications

Dietary cholesterol increases paraoxonase 1 enzyme activity

Dietary cholesterol increases paraoxonase 1 enzyme activity

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients

The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field

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