Semi-Quantitative Multiplex Profiling of the Complement System Identifies Associations of Complement Proteins with Genetic Variants and Metabolites in Age-Related Macular Degeneration.

Autor:	Acar IE; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Willems E; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Kersten E; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Keizer-Garritsen J; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Kragt E; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Bakker B; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Galesloot TE; Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Hoyng CB; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Fauser S; Roche Pharma Research and Early Development, Roche Innovation Center Basel, 124 Grenzacherstrasse, 4070 Basel, Switzerland., van Gool AJ; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Lechanteur YTE; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Koertvely E; Roche Pharma Research and Early Development, Roche Innovation Center Basel, 124 Grenzacherstrasse, 4070 Basel, Switzerland., Nogoceke E; Roche Pharma Research and Early Development, Roche Innovation Center Basel, 124 Grenzacherstrasse, 4070 Basel, Switzerland., Gloerich J; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., de Jonge MI; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Lorés-Motta L; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Roche Pharma Research and Early Development, Roche Innovation Center Basel, 124 Grenzacherstrasse, 4070 Basel, Switzerland., den Hollander AI; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of personalized medicine [J Pers Med] 2021 Nov 25; Vol. 11 (12). Date of Electronic Publication: 2021 Nov 25.
DOI:	10.3390/jpm11121256
Abstrakt:	Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. The complement system has been identified as one of the main AMD disease pathways. We performed a comprehensive expression analysis of 32 complement proteins in plasma samples of 255 AMD patients and 221 control individuals using mass spectrometry-based semi-quantitative multiplex profiling. We detected significant associations of complement protein levels with age, sex and body-mass index (BMI), and potential associations of C-reactive protein, factor H related-2 (FHR-2) and collectin-11 with AMD. In addition, we confirmed previously described associations and identified new associations of AMD variants with complement levels. New associations include increased C4 levels for rs181705462 at the C2 / CFB locus, decreased vitronectin (VTN) levels for rs11080055 at the TMEM97 / VTN locus and decreased factor I levels for rs10033900 at the CFI locus. Finally, we detected significant associations between AMD-associated metabolites and complement proteins in plasma. The most significant complement-metabolite associations included increased high density lipoprotein (HDL) subparticle levels with decreased C3, factor H (FH) and VTN levels. The results of our study indicate that demographic factors, genetic variants and circulating metabolites are associated with complement protein components. We suggest that these factors should be considered to design personalized treatment approaches and to increase the success of clinical trials targeting the complement system.
Databáze:	MEDLINE
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