title: Delineation of concentration ranges and longitudinal changes of human plasma protein variants.
abstract: 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.
authors: Molecular Biomarkers Laboratory at the Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America; Intrinsic Bioprobes, Tempe, Arizona, United States of America.
authors: Olgica
authors: O
authors: Trenchevska
authors: Intrinsic Bioprobes, Tempe, Arizona, United States of America.
authors: David A
authors: DA
authors: Phillips
authors: Molecular Biomarkers Laboratory at the Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors: Randall W
authors: RW
authors: Nelson
authors: Molecular Biomarkers Laboratory at the Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America; Intrinsic Bioprobes, Tempe, Arizona, United States of America; Institute for Population Proteomics, Tempe, Arizona, United States of America.
authors: Dobrin
authors: D
authors: Nedelkov
mesh_terms: D000328:Adult; D000367:Age Factors; D001798:Blood Proteins / Q000378:metabolism*; D055316:Cystatin C / Q000378:metabolism; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008970:Molecular Weight; D050505:Mutant Proteins / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism*; D011228:Prealbumin / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012016:Reference Values; D012177:Retinol-Binding Proteins / Q000378:metabolism; D013714:Tennessee; D013781:Texas; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D055316:Cystatin C; D050505:Mutant Proteins; D011228:Prealbumin; D020033:Protein Isoforms; D012177:Retinol-Binding Proteins; D001613:beta 2-Microglobulin