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Your search keyword '"Ajana, S."' showing total 4 results
Start Over Author "Ajana, S." Topic metabolomics
4 results on '"Ajana, S."'

1. Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration: The EYE-RISK Consortium.

Author

Acar İE, Lores-Motta L, Colijn JM, Meester-Smoor MA, Verzijden T, Cougnard-Gregoire A, Ajana S, Merle BMJ, de Breuk A, Heesterbeek TJ, van den Akker E, Daha MR, Claes B, Pauleikhoff D, Hense HW, van Duijn CM, Fauser S, Hoyng CB, Delcourt C, Klaver CCW, Galesloot TE, and den Hollander AI

Subjects
ATP Binding Cassette Transporter 1 genetics, Aged, Aged, 80 and over, Apolipoproteins E genetics, Case-Control Studies, Cholesterol Ester Transfer Proteins genetics, Female, Humans, Lipase genetics, Male, Metabolome genetics, Middle Aged, Proton Magnetic Resonance Spectroscopy, Complement Activation physiology, Genomics, Macular Degeneration genetics, Metabolomics
Abstract

Purpose: The current study aimed to identify metabolites associated with age-related macular degeneration (AMD) by performing the largest metabolome association analysis in AMD to date, as well as aiming to determine the effect of AMD-associated genetic variants on metabolite levels and investigate associations between the identified metabolites and activity of the complement system, one of the main AMD-associated disease pathways., Design: Case-control association analysis of metabolomics data., Participants: Five European cohorts consisting of 2267 AMD patients and 4266 control participants., Methods: Metabolomics was performed using a high-throughput proton nuclear magnetic resonance metabolomics platform, which allows quantification of 146 metabolite measurements and 79 derivative values. Metabolome-AMD associations were studied using univariate logistic regression analyses. The effect of 52 AMD-associated genetic variants on the identified metabolites was investigated using linear regression. In addition, associations between the identified metabolites and activity of the complement pathway (defined by the C3d-to-C3 ratio) were investigated using linear regression., Main Outcome Measures: Metabolites associated with AMD., Results: We identified 60 metabolites that were associated significantly with AMD, including increased levels of large and extra-large high-density lipoprotein (HDL) subclasses and decreased levels of very low-density lipoprotein (VLDL), amino acids, and citrate. Of 52 AMD-associated genetic variants, 7 variants were associated significantly with 34 of the identified metabolites. The strongest associations were identified for genetic variants located in or near genes involved in lipid metabolism (ABCA1, CETP, APOE, and LIPC) with metabolites belonging to the large and extra-large HDL subclasses. Also, 57 of 60 metabolites were associated significantly with complement activation levels, independent of AMD status. Increased large and extra-large HDL levels and decreased VLDL and amino acid levels were associated with increased complement activation., Conclusions: Lipoprotein levels were associated with AMD-associated genetic variants, whereas decreased essential amino acids may point to nutritional deficiencies in AMD. We observed strong associations between the vast majority of the AMD-associated metabolites and systemic complement activation levels, independent of AMD status. This may indicate biological interactions between the main AMD disease pathways and suggests that multiple pathways may need to be targeted simultaneously for successful treatment of AMD., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Published
2020
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2. Metabolomics in serum of patients with non-advanced age-related macular degeneration reveals aberrations in the glutamine pathway.

Author

Kersten E, Dammeier S, Ajana S, Groenewoud JMM, Codrea M, Klose F, Lechanteur YT, Fauser S, Ueffing M, Delcourt C, Hoyng CB, de Jong EK, and den Hollander AI

Subjects
Aged, Discriminant Analysis, Female, Humans, Least-Squares Analysis, Macular Degeneration genetics, Macular Degeneration pathology, Metabolic Networks and Pathways genetics, Middle Aged, Biomarkers blood, Glutamine metabolism, Macular Degeneration blood, Metabolomics
Abstract

Age-related macular degeneration (AMD) is a common, progressive multifactorial vision-threatening disease and many genetic and environmental risk factors have been identified. The risk of AMD is influenced by lifestyle and diet, which may be reflected by an altered metabolic profile. Therefore, measurements of metabolites could identify biomarkers for AMD, and could aid in identifying high-risk individuals. Hypothesis-free technologies such as metabolomics have a great potential to uncover biomarkers or pathways that contribute to disease pathophysiology. To date, only a limited number of metabolomic studies have been performed in AMD. Here, we aim to contribute to the discovery of novel biomarkers and metabolic pathways for AMD using a targeted metabolomics approach of 188 metabolites. This study focuses on non-advanced AMD, since there is a need for biomarkers for the early stages of disease before severe visual loss has occurred. Targeted metabolomics was performed in 72 patients with early or intermediate AMD and 72 control individuals, and metabolites predictive for AMD were identified by a sparse partial least squares discriminant analysis. In our cohort, we identified four metabolite variables that were most predictive for early and intermediate stages of AMD. Increased glutamine and phosphatidylcholine diacyl C28:1 levels were detected in non-advanced AMD cases compared to controls, while the rate of glutaminolysis and the glutamine to glutamate ratio were reduced in non-advanced AMD. The association of glutamine with non-advanced AMD corroborates a recent report demonstrating an elevated glutamine level in early AMD using a different metabolomics technique. In conclusion, this study indicates that metabolomics is a suitable method for the discovery of biomarker candidates for AMD. In the future, larger metabolomics studies could add to the discovery of novel biomarkers in yet unknown AMD pathways and expand our insights in AMD pathophysiology., Competing Interests: The commercial affiliation of S.F. to La Roche AG does not alter our adherence to PLOS ONE policies on sharing data and materials.

Published
2019
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3. Integrating metabolomics, genomics and disease pathways in age-related macular degeneration: The EYE-RISK Consortium

Author

Acar, I.E., Lores-Motta, L., Colijn, J.M., Meester-Smoor, M.A., Verzijden, T., Cougnard-Gregoire, A., Ajana, S., Merle, B.M.J., Breuk, A. de, Heesterbeek, T.J., Akker, E. van den, Daha, M.R., Claes, B., Pauleikhoff, D., Hense, H.W., Duijn, C.M. van, Fauser, S., Hoyng, C.B., Delcourt, C., Klaver, C.C.W., Galesloot, T.E., Hollander, A.I. den, and EYE-RISK Consortium

Subjects
Aged, 80 and over, Male, genetic structures, Proton Magnetic Resonance Spectroscopy, Genomics, Lipase, Middle Aged, eye diseases, Cholesterol Ester Transfer Proteins, Macular Degeneration, Apolipoproteins E, Case-Control Studies, Metabolome, Humans, Metabolomics, Female, sense organs, Complement Activation, ATP Binding Cassette Transporter 1, Aged
Abstract

Objective In the current study we aimed to identify metabolites associated with age-related macular degeneration (AMD) by performing the largest metabolome association analysis in AMD to date. In addition, we aimed to determine the effect of AMD-associated genetic variants on metabolite levels, and aimed to investigate associations between the identified metabolites and activity of the complement system, one of the main AMD-associated disease pathways. Design Case-control assocation analysis of metabolomics data. Subjects 2,267 AMD cases and 4,266 controls from five European cohorts. Methods Metabolomics was performed using a high-throughput H-NMR metabolomics platform, which allows the quantification of 146 metabolite measurements and 79 derivative values. Metabolome-AMD associations were studied using univariate logistic regression analyses. The effect of 52 AMD-associated genetic variants on the identified metabolites was investigated using linear regression. In addition, associations between the identified metabolites and activity of the complement pathway (defined by the C3d/C3 ratio) were investigated using linear regression. Main Outcome Measures Metabolites associated with AMD Results We identified 60 metabolites that were significantly associated with AMD, including increased levels of large and extra-large HDL subclasses and decreased levels of VLDL, amino acids and citrate. Out of 52 AMD-associated genetic variants, seven variants were significantly associated with 34 of the identified metabolites. The strongest associations were identified for genetic variants located in or near genes involved in lipid metabolism (ABCA1, CETP, APOE, LIPC) with metabolites belonging to the large and extra-large HDL subclasses. In addition, 57 out of 60 metabolites were significantly associated with complement activation levels, and these associations were independent of AMD status. Increased large and extra-large HDL levels and decreased VLDL and amino acid levels were associated with increased complement activation. Conclusions Lipoprotein levels were associated with AMD-associated genetic variants, while decreased essential amino acids may point to nutritional deficiencies in AMD. We observed strong associations between the vast majority of the AMD-associated metabolites and systemic complement activation levels, independent of AMD status. This may indicate biological interactions between the main AMD disease pathways, and suggests that multiple pathways may need to be targeted simultaneously for successful treatment of AMD. Abbreviations AMDAge-related macular degenerationGWASGenome-wide association studyHDLHigh density lipoproteinVLDLVery low density lipoproteinNMRNuclear magnetic resonanceACMEAverage casual effect estimatesOROdds ratiopFDRFalse discovery rate corrected p-valueCIConfindence intervalCVDCardiovascular diseasesPCAPrincipal component analysisSDStandard deviationBMIBody mass indexFDRFalse discovery rateEUGENDAEuropean Genetic DatabaseRSRotterdam StudyALIENORAntioxydants, LIpides Essentiels, Nutrition et maladies OculaiResCORRBICombined Ophthalmic Research Rotterdam BiobankMARSMünster Age and Retina Study. For all metabolite abbreviations please see supplementary table 2

Published
2020

4. Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia

Author

Colijn, J. M., Verzijden, T., Meester-Smoor, M. A., Klaver, C. C. W., Demirkan, A., Ahmad, S., van Duijn, C. M., den Hollander, A. I., Kersten, E., Hoyng, C. B., Cougnard-Gregoire, A., Merle, B. M. J., Korobelnik, J. -F., Delcourt, C., Papageorgiou, G., Mulder, M. T., Costa, M. A., Silva, R., Benlian, P., Bertelsen, G., Bron, A. M., Creuzot-Garcher, C., Claes, B., Hense, H. -W., Erke, M. G., Fauser, S., Foster, P. J., Khawaja, A. P., Hammond, C. J., Williams, K. M., Piermarocchi, S., Segato, T., Souied, E. H., Acar, N., Altay, L., Anastosopoulos, E., Azuara-Blanco, A., Berendschot, T., Bergen, A., Binquet, C., Bird, A., Bobak, M., Larsen, M. B., Boon, C., Bourne, R., Bretillon, L., Broe, R., Bron, A., Buitendijk, G., Cachulo, M. L., Capuano, V., Carriere, I., Chakravarthy, U., Chan, M., Chang, P., Colijn, J., Cree, A., Cumberland, P., Cunha-Vaz, J., Daien, V., De Jong, E., Deak, G., Delyfer, M. -N., Hollander, A. D., Dietzel, M., Faria, P., Farinha, C., Finger, R., Fletcher, A., Foster, P., Founti, P., Gorgels, T., Grauslund, J., Grus, F., Hammond, C., Heesterbeek, T., Hermann, M., Hoehn, R., Hogg, R., Holz, F., Hoyng, C., Jansonius, N., Janssen, S., de Jong, E., Khawaja, A., Klaver, C., Lamparter, J., Le Goff, M., Lehtimaki, T., Leung, I., Lotery, A., Mauschitz, M., Meester, M., Merle, B., Meyer zu Westrup, V., Midena, E., Miotto, S., Mirshahi, A., Mohan-Said, S., Mueller, M., Muldrew, A., Murta, J., Nickels, S., Nunes, S., Owen, C., Peto, T., Pfeiffer, N., Prokofyeva, E., Rahi, J., Raitakari, O., Rauscher, F., Ribeiro, L., Rougier, M. -B., Rudnicka, A., Randjvar, Sahel, Salonikiou, A., Sanchez, C., Schick, T., Schmitz-Valckenberg, S., Schuster, A., Schweitzer, C., Shehata, J., Silvestri, G., Simader, C., Souied, E., Speckauskas, M., Springelkamp, H., Tapp, R., Topouzis, F., van Leeuwen, E., Verhoeven, V., Vingerling, H., Von Hanno, T., Williams, K., Wolfram, C., Yip, J., Zerbib, J., Ajana, S., Arango-Gonzalez, B., Arndt, V., Bhatia, V., Bhattacharya, S. S., Biarnes, M., Borrell, A., Buhren, S., Calado, S. M., Dammeier, S., de Jong, E. K., De la Cerda, B., Diaz-Corrales, F. J., Diether, S., Emri, E., Endermann, T., Ferraro, L. L., Garcia, M., Heesterbeek, T. J., Honisch, S., Kilger, E., Langen, H., Lengyel, I., Luthert, P., Maugeais, C., Meester-Smoor, M., Merle Inserm, B. M. J., Mones, J., Nogoceke, E., Pool, F. M., Rodriguez, E., Ueffing, M., Ulrich Bartz-Schmidt, K. U., van Leeuwen, E. M., and Zumbansen, M.

Subjects
Male, Magnetic Resonance Spectroscopy, HDL, genetic structures, European Continental Ancestry Group, Polymorphism, Single Nucleotide, White People, LDL, Macular Degeneration, Risk Factors, 80 and over, Odds Ratio, Humans, Metabolomics, European Union, Polymorphism, Triglycerides, Aged, Aged, 80 and over, Cholesterol, HDL, Single Nucleotide, Cholesterol, LDL, Middle Aged, Lipid Metabolism, eye diseases, Cholesterol Ester Transfer Proteins, Cholesterol, Cross-Sectional Studies, lipids (amino acids, peptides, and proteins), Female, sense organs
Abstract

Purpose Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design Pooled analysis of cross-sectional data. Participants Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures AMD features and stage; lipid measurements. Results HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10–7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10–6 and P = 1.6 × 10–4). Conclusions Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.

Published
2018

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