Study of the expression of the genetic variants of human alpha1-acid glycoprotein in healthy subjects using isoelectric focusing and immunoblotting.
Human alpha1-acid glycoprotein (AAG) exists as an heterogeneous population of two or three genetic variants (ORM1 F1 and/or S and ORM2 A) in the plasma of most individuals. The ORM1 and ORM2 variants have a separate genetic origin. AAG belongs to the acute-phase proteins, which, under conditions of inflammation, increase several-fold in concentration. Additionally, there is evidence to suggest that it is not only the concentration but also the distribution of the two gene products of AAG (ORM1 and ORM2) that alter in such conditions. Variations of the relative concentrations of the AAG variants in certain diseases, such as cancer, can only be shown by reference to data collected in healthy people. In this study, we have investigated a group of 74 healthy subjects (42 men and 32 women) for AAG concentrations, AAG phenotypes and relative proportions of genetic variants in plasma. The specific assay of AAG was carried out by an immunonephelometric method and the phenotyping was performed, after desialylation of AAG, by analytical isoelectric focusing. Detection of the AAG variants was made by immunoblotting and their relative proportions were determined by laser densitometry analysis. The AAG plasma concentrations in the healthy group ranged between 0.28 and 0.92 g/l (mean value 0.50+/-0.14 g/l). The relative proportions of the variants derived from the two genes of AAG were variable, depending on the individual, but the amount of ORM1 variants almost always exceeded that of the ORM2 variant. No sex-related differences were observed in respect either in the total AAG level nor the relative proportions of the ORM1 and ORM2 variants. The data collected in this study may serve as a reference towards the investigation of possible changes in the expression of the genetic variants of AAG in chronic inflammatory diseases.
Duché
J C
JC
Service Hospitalo-Universitaire de Pharmacologie, Centre Hospitalier Intercommunal de Créteil, France.
Hervé
F
F
Tillement
J P
JP
D000328:Adult; D000368:Aged; D015153:Blotting, Western / Q000379:methods*; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009961:Orosomucoid / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values
D009961:Orosomucoid