Targeted MRM assay Complement System AMD cohort
Acar IE, Willems E, Kersten E, Keizer-Garritsen J, Kragt E, Bakker B, Galesloot TE, Hoyng CB, Fauser S, van Gool AJ, Lechanteur YTE, Koertvely E, Nogoceke E, Gloerich J, de Jonge MI, Lorés-Motta L, den Hollander AI. Semi-Quantitative Multiplex Profiling of the Complement System Identifies Associations of Complement Proteins with Genetic Variants and Metabolites in Age-Related Macular Degeneration. Vol. 11, Journal of Personalized Medicine . 2021
- Organism: Homo sapiens
- Instrument: Xevo TQ-S
- SpikeIn:
Yes
- Keywords:
Age-related macular degeneration, AMD, complement system, quantitative multiplex profiling, mass spectrometry, C4, vitronectin, factor I, genetic variants, metabolites, HDL
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Lab head: Jolein Gloerich
Submitter: Esther Willems
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 quantitative multiplex profiling. We detected significant associations of complement protein levels with age, gender 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 taken into account to design personalized treatment approaches and to increase the success of clinical trials targeting the complement system.
Multiplex targeted mass spectrometry profiling of 32 complement protein levels in 255 AMD patients and 221 healthy individuals.
Created on 8/2/21, 11:05 PM