Normal Alpha-1-Antitrypsin Variants Display in Serum Allele-Specific Protein Levels.
J Proteome Res
; 22(4): 1331-1338, 2023 04 07.
Article
em En
| MEDLINE
| ID: mdl-36946534
ABSTRACT
Alpha-1-antitrypsin (A1AT or SERPINA1) has been proposed as a putative biomarker distinguishing healthy from diseased donors throughout several proteomics studies. However, the SERPINA1 gene displays high variability of frequent occurring genotypes among the general population. These different genotypes may affect A1AT expression and serum protein concentrations, and this is often not known, ignored, and/or not reported in serum proteomics studies. Here, we address allele-specific protein serum levels of A1AT in donors carrying the normal M variants of A1AT by measuring the proteoform profiles of purified A1AT from 81 serum samples, originating from 52 donors. When focusing on heterozygous donors, our data clearly reveal a statistically relevant difference in allele-specific protein serum levels of A1AT. In donors with genotype PI*M1VM1A, the experimentally observed ratio was approximately 11 (M1V/M1A, 1.000.96 ± 0.07, n = 17). For individuals with genotype PI*M1VM2, this ratio was 11.28 (M1V/M2, 1.001.31, ±0.19, n = 7). For genotypes PI*M1VM3 and PI*M1AM3, a significant higher amount of M3 was observed compared to the M1-subtypes (M1V/M3, 1.001.84 ± 0.35, n = 8; M1A/M3, 1.001.61 ± 0.33, n = 5). We argue that these observations are important and should be considered when analyzing serum A1AT levels before proposing A1AT as a putative serum biomarker.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiência de alfa 1-Antitripsina
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article