Delineation of concentration ranges and longitudinal changes of human plasma protein variants

• Published in: PloS one Vol. 9; no. 6; p. e100713
• Main Authors: Trenchevska, Olgica, Phillips, David A, Nelson, Randall W, Nedelkov, Dobrin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.06.2014; Public Library of Science (PLoS)
• Subjects: Adult; Age Factors; Alternative splicing; Amino acids; beta 2-Microglobulin - metabolism; Binding proteins; Biology and Life Sciences; Biomarkers; Blood plasma; Blood proteins; Blood Proteins - metabolism; Cystatin C; Cystatin C - metabolism; Female; Humans; Immunoassay; Immunoassays; Immunoglobulins; In vivo methods and tests; Laboratories; Longitudinal Studies; Male; Mass spectrometry; Molecular Weight; Mutant Proteins - metabolism; Occupational health; Peptides; Physical Sciences; Plasma; Plasma - metabolism; Population; Prealbumin - metabolism; Protein binding; Protein Isoforms - metabolism; Proteins; Proteomics; Reference Values; Research and Analysis Methods; Retinoids; Retinol-Binding Proteins - metabolism; Rheumatoid arthritis; Scientific imaging; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Spectrometry; Tennessee; Texas; Transthyretin; Vitamin A; Tennessee; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100713

Human protein diversity arises as a result of alternative splicing, single nucleotide polymorphisms (SNPs) and posttranslational modifications. Because of these processes, each protein can exists as multiple variants in vivo. Tailored strategies are needed to study these protein variants and understand their role in health and disease. In this work we utilized quantitative mass spectrometric immunoassays to determine the protein variants concentration of beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin, in a population of 500 healthy individuals. Additionally, we determined the longitudinal concentration changes for the protein variants from four individuals over a 6 month period. Along with the native forms of the four proteins, 13 posttranslationally modified variants and 7 SNP-derived variants were detected and their concentration determined. Correlations of the variants concentration with geographical origin, gender, and age of the individuals were also examined. This work represents an important step toward building a catalog of protein variants concentrations and examining their longitudinal changes.