Association of HDL-Related Loci with Age-Related Macular Degeneration and Plasma Lutein and Zeaxanthin: the Alienor Study

Merle, Bénédicte M. J.; Maubaret, C.; Korobelnik, J.-F.; Delyfer, M.-N.; Rougier, M.–B.; Lambert, Jean‐Charles; Amouyel, Philippe; Malet, Florence; Goff, Mélanie Le; Dartigues, Jean François; Barberger‐Gateau, Pascale; Delcourt, Cécile

doi:10.1371/journal.pone.0079848

Cited by 40 publications

(36 citation statements)

References 49 publications

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“…Also, there were two studies which have got opposite results and proved significant association between LIPC (rs493258) and AMD development [26,27]. It should be noted, that we are in agreement with these six studies [11,12,18,19,21,22], which found that LIPC gene polymorphisms (rs10468017, rs493258) may reduce possibility for AMD development. Reynolds et al investigated 458 participants study, including 318 advanced AMD cases with either geographic atrophy (n=123) or neovascular AMD (n=195), and 140 controls [12].…”

Section: Discussionsupporting

confidence: 87%

“…Our results showed a protective role of these three gene polymorphisms: LIPC rs10468017 polymorphism decreased risk of both forms of AMD (early and exudative), LIPC rs493258 polymorphism decreased risk only of Regarding the results analyzing LIPC gene polymorphisms association with AMD, six studies found that LIPC gene can slow down AMD development [11,12,18,19,21,22]. Among these six studies, two studies analyzed LIPC (rs10468017) gene polymorphism [12,21] and three LIPC (rs493258) [11,18,22], while one study analyzed both gene polymorphisms [19]. Four studies found no association with AMD [16,17,23,24], two studies analyzed only rs10468017 polymorphism association with AMD [16,17] and two other studies analyzed both LIPC gene polymorphisms [23,24].…”

Section: Discussionmentioning

confidence: 54%

“…No association was found with LIPL rs10468017 gene polymorphism and AMD [17]. On the other hand other four studies [16,17,23,24] deny results, and are in conflict with the previuos studies, which proved possible risk-reducing effect on AMD development [11,12,18,19,21,22]. One study revealed rs10468017 in LIPC being associated with a decreased risk of progression from large drusen to NV [25], but it seems that this study can be in agreement with the previous six studies, which found that LIPC rs10468017 can decrease AMD development.…”

Section: Discussionmentioning

confidence: 93%

“…Genotype-phenotype associations are known to vary from country to country (11)(12)(13)(14)(15)(16)(17)(18)(19), so the aim of our study was to determine the genotype frequency of LIPC rs10468017, rs493258 and LPL rs126789919 in patients with early and exudative AMD in Lithuanian subjects.…”

Section: Journal Of Clinical and Experimental Ophthalmologymentioning

confidence: 99%

“…This enzyme is found on the surface of capillary cells which play a key role in the digestion and However, results of studies related to AMD in different cohorts on the reported HDL cholesterol metabolism genes, including the hepatic lipase (LIPC) and lipoprotein lipase (LPL) genes are inconsistent [12,[16][17][18][19]. Some studies did not find associations between these genes and AMD [16,17], while other studies found associations with AMD [18]. …”

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confidence: 99%

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LIPC rs10468017, rs493258 and LPL rs12678919 Role in Patients With Age- Related Macular Degeneration

Liutkevičienė¹,

Vilkeviciute²,

Streleckiene³

et al. 2017

J Clin Exp Ophthalmol

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Objective: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly individuals in developed countries. The etiology and pathophysiology of AMD are not fully understood. Formation of drusen is the main pathological change in AMD. Lipids make up about 40% of drusen volume, thus possible relation between AMD and genes controlling lipid metabolism could provide novel insights into AMD. Our purpose was to determine the genotype frequencies of LIPC rs10468017, rs493258 and LPL rs126789919 in patients with AMD in Lithuanian population. Methods:The study enrolled 279 patients with early AMD, 256 patients with exudative AMD, and 829 healthy controls (reference group). The genotyping was carried out using the RT-PCR.Results: LIPC rs10468017 polymorphism was associated with a decreased risk of early and exudative AMD, while LPL rs126789919 polymorphism was associated with a decreased risk of exudative AMD and LIPC rs493258 was only associated with a decreased risk of early AMD. Conclusion:The study showed that LIPC rs10468017, rs493258 and LPL rs126789919 gene polymorphisms may have a protective role in AMD development.Keywords: Age-related macular degeneration; LIPC rs10468017; LIPC rs493258; LPL rs126789919; Gene polymorphism; Early AMD; Exudative AMD; Lipid metabolism IntroductionAge-related macular degeneration (AMD) is a degenerative disease affecting central part of the retina (macula). Half of the blindness cases in industrialized countries are AMD related [1]. This disease affects 2.5 million persons in Europe, and 1.75 million in the USA [2,3]. About 13.8% of population in Lithuania is also affected by AMD. AMD is a complex disease with many contributing factors: age, oxidative stress, inflammatory processes, genetic factors and others as well as their interrelationship [4].Aging process causes changes in human retina such as the appearance of drusen, an ophthalmoscopically visible focal yellow deposition of acellular polymorphous debris between the retinal pigment epithelium and Bruch's membrane [5]. In early AMD, a large number (≤ 10) of drusen result in diffuse regions with hyperpigmentation or hypopigmentation [6,7]. Late form of AMD is classified into dry (geographic atrophy of the retinal pigment epithelium with the lack of neovascularization areas) and wet type (or exudative; new blood vessel formations in choroid, called the choroidal neovascularization areas, further leading to the formation of the disciform scars) [6]. The wet form of AMD causes more severe damage to the retina and more frequently leads to devastating consequences, such as vision loss, than the dry form of AMD [6,7].In drusen lipids represent at least 40% of the volume [8]. Thus, lipid metabolism and particularly high-density lipoprotein may be involved in the pathogenic mechanism of AMD [8]. Lipid particles accumulate within Bruch's membrane prior to the development of basal deposits or drusen. This observation has led to the hypothesis that these lipid particles contribute to drusen formation dur...

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 93%

Section: Journal Of Clinical and Experimental Ophthalmologymentioning

confidence: 99%

mentioning

confidence: 99%

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LIPC rs10468017, rs493258 and LPL rs12678919 Role in Patients With Age- Related Macular Degeneration

Liutkevičienė¹,

Vilkeviciute²,

Streleckiene³

et al. 2017

J Clin Exp Ophthalmol

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Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment

et al. 2017

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IMPORTANCE Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD).OBJECTIVES To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD. DESIGN, SETTING, AND PARTICIPANTSThis study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD.INTERVENTIONS Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. MAIN OUTCOMES AND MEASURESThe primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98°eccentricity. The statistical analysis was adjusted for hospital and for risk factors.RESULTS Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98°eccentricity between 6 months and baseline was 0.036 (95% CI, −0.037 to 0.110) (P = .33).CONCLUSIONS AND RELEVANCE Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01269697

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Incidence and Risk Factors of Reticular Pseudodrusen Using Multimodal Imaging

et al. 2020

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IMPORTANCE Although retinal multimodal imaging is needed for diagnosing reticular pseudodrusen (RPD), the incidence of RPD in the general population typically has been assessed only using fundus photographs, which may underestimate their incidence.OBJECTIVES To describe the incidence of RPD using retinal color photographs, spectral-domain optical coherence tomography scans, fundus autofluorescence, and near-infrared reflectance images among individuals 77 years of age or older and to analyze the associated risk factors of RPD. DESIGN, SETTING, AND PARTICIPANTSThe ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires) Study is a cohort of French individuals 77 years of age or older. Data for this study were collected between February 22, 2011, and February 15, 2017, with a mean (SD) follow-up of 3.7 (1.0) years (range, 1.2-5.6 years). At baseline, 501 individuals were eligible to participate. Of 1002 eyes, 197 had prevalent RPD, advanced age-related macular degeneration, or ungradable images. Of the remaining 805 eyes, 333 were missing follow-up data; therefore, the statistical analyses included data from 472 eyes. Data management and statistical analyses were performed between March 15, 2017, and April 5, 2019. MAIN OUTCOMES AND MEASURESReticular pseudodrusen were considered as present if detected by at least 2 of the following imaging methods: color fundus photographs, fundus autofluorescence, near-infrared reflectance, and spectral-domain optical coherence tomography images. RESULTSOf the 472 eyes analyzed, 263 (55.7%) were from female participants, and the mean (SD) age was 81.9 (3.2) years. Forty-three eyes developed RPD, corresponding to an annual incidence rate of 2.9% (95% CI, 1.9%-4.4%) per participant and an estimated 5-year risk of 13.5%. In multivariable analysis, 4 risk factors of incident RPD were identified: subfoveal choroidal thinning (hazard ratio [HR], 0.99; 95% CI, 0.99-1.00 per 10-μm decrease in thickness; P = .02) and the presence of the minor allelic variants rs10490924 for ARMS2 (HR, 3.57; 95% CI, 1.80-7.10; P < .001), rs1061170 for CFH (HR, 2.12; 95% CI, 1.02-4.41; P = .04), and rs10468017 for LIPC (HR, 2.57; 95% CI, 1.37-4.82; P = .003). Lipophilic statin therapy was associated with a lower incidence of RPD (HR, 0.13; 95% CI, 0.02-0.74; P = .02). CONCLUSIONS AND RELEVANCEWith the use of multimodal imaging, the RPD incidence rate was higher than previously reported in other population-based studies using fundus color images. Individuals with subfoveal choroidal thinning or carrying minor allelic variants for ARMS2, CFH, or LIPC had an increased risk for RPD, whereas lipophilic statin therapy was associated with a lower incidence.

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Association of HDL-Related Loci with Age-Related Macular Degeneration and Plasma Lutein and Zeaxanthin: the Alienor Study

Cited by 40 publications

References 49 publications

LIPC rs10468017, rs493258 and LPL rs12678919 Role in Patients With Age- Related Macular Degeneration

LIPC rs10468017, rs493258 and LPL rs12678919 Role in Patients With Age- Related Macular Degeneration

Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment

Incidence and Risk Factors of Reticular Pseudodrusen Using Multimodal Imaging

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