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利用等电聚焦和免疫印迹法研究健康受试者中人类α1-酸性糖蛋白基因变体的表达。

Study of the expression of the genetic variants of human alpha1-acid glycoprotein in healthy subjects using isoelectric focusing and immunoblotting.

作者信息

Duché J C, Hervé F, Tillement J P

机构信息

Service Hospitalo-Universitaire de Pharmacologie, Centre Hospitalier Intercommunal de Créteil, France.

出版信息

J Chromatogr B Biomed Sci Appl. 1998 Sep 11;715(1):103-9. doi: 10.1016/s0378-4347(98)00084-x.

DOI:10.1016/s0378-4347(98)00084-x
PMID:9792502
Abstract

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.

摘要

人类α1-酸性糖蛋白(AAG)在大多数个体的血浆中以两种或三种遗传变体(ORM1 F1和/或S以及ORM2 A)的异质群体形式存在。ORM1和ORM2变体有各自独立的遗传起源。AAG属于急性期蛋白,在炎症条件下,其浓度会增加几倍。此外,有证据表明,在这种情况下,不仅AAG的浓度会改变,其两种基因产物(ORM1和ORM2)的分布也会改变。只有参照健康人收集的数据,才能显示出某些疾病(如癌症)中AAG变体相对浓度的变化。在本研究中,我们调查了一组74名健康受试者(42名男性和32名女性)的血浆AAG浓度、AAG表型以及遗传变体的相对比例。通过免疫比浊法对AAG进行特异性检测,并在AAG去唾液酸化后,通过分析等电聚焦进行表型分析。通过免疫印迹检测AAG变体,并通过激光密度分析确定其相对比例。健康组的血浆AAG浓度在0.28至0.92 g/l之间(平均值0.50±0.14 g/l)。源自AAG两个基因的变体的相对比例因人而异,但ORM1变体的量几乎总是超过ORM2变体。在总AAG水平以及ORM1和ORM2变体的相对比例方面,未观察到性别相关差异。本研究收集的数据可作为参考,用于调查慢性炎症性疾病中AAG遗传变体表达的可能变化。

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