Disease relevance of ORM1

• The results suggest that the ORM1 1 and HP1 types may be contributory determinants in the multifactorial etiology of sarcoidosis [1].
• In previous studies, the ORM1 1 type has been found to be associated with psoriasis and sarcoidosis, presumably by influencing the progression and clinical course of these disorders [2].
• In this report, a significant association between the ORM1 1 type and allergic contact dermatitis in male patients (relative risk = 1.9, 95% confidence interval = 1.0-3.6) is presented [2].
• The ORM1 phenotype showed a significant increase in sarcoidosis (RR = 1.34, p = 0.036), which was more pronounced among patients with low (< 1,500 nkat/l) angiotensin-converting enzyme levels (RR = 1.83, p = 0.00065) and hypercalcemia (RR = 3.69, p = 0.0023) [1].
• The major component of human alpha 1-acid glycoprotein found in plasma is coded by AGP-A, which is expressed in liver and in hepatoma cell lines and is induced by inflammatory stimuli [3].

Psychiatry related information on ORM1

• Using the sib-pair methods, evidence for linkage was found with orosomucoid (ORM) on chromosome 9q (p = 0.006), regardless of whether only individuals with unipolar depression, alcoholism, or antisocial personality were considered to be affected, or whether individuals with any psychiatric disorder were considered to be affected [4].
• At 50 micrograms/ml concentration of orosomucoid, the lymphocyte activation was found in randomly selected blood donors which included normal healthy volunteers and patients with T cell immunodeficiency or Alzheimer's disease, demonstrating a consistent immunostimulatory action of this glycoprotein [5].
• METHODS: The current study compared decision-making strategies on the basis of a combination of disease indices and serum concentrations of orosomucoid (strategy A) and disease indices only (strategy B) for the tapering of prednisolone [6].
• In the females the main factors were age, orosomucoid, and hemoglobin in all age groups, MCV and tobacco in females less than 20 years old, and ferritin and physical activity in females more than 20 years old [7].
• Plasma levels of complement factors 3 and 4, orosomucoid and opsonic functions in anorexia nervosa [8].

High impact information on ORM1

• During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012) [9].
• The alpha-1 acid glycoprotein (orosomucoid; AAG) is a normal constituent of human plasma (650+/-215 microgram ml(-1)) which increases in concentration as much as fivefold in associations with acute inflammation and cancer, and thus is recognized as an acute phase protein [10].
• The human genome contains three alpha 1-glycoprotein genes (AGP-A, AGP-B, and AGP-B') encoding for slightly different forms of the protein [3].
• We have studied the regulation of the cloned AGP-A gene by transfection into cell lines of hepatic and nonhepatic origin [3].
• Inflammation-induced expression of sialyl Lewis X-containing glycan structures on alpha 1-acid glycoprotein (orosomucoid) in human sera [11].

Chemical compound and disease context of ORM1

• We report significant associations between ORM1 and C3 types in sarcoidosis and breast cancer, but not in healthy individuals [12].
• The purpose of this study was to evaluate the influence of three sialic acid rich glycoproteins (orosomucoid, haptoglobin, and alpha1-antitrypsin) on the relationship between S-TSA and carotid atherosclerosis [13].
• The proteinuria rate and the relative clearances of beta 2-microglobulin, orosomucoid, albumin, transferrin and IgG were measured in forty-two workers exposed to cadmium and in seventy-seven control workers [14].
• Levels of orosomucoid, a1-antitrypsin, C1-inhibitor and von Willebrand factor did not change during treatment showing that the increase of haptoglobin was not due to an acute-phase response [15].
• Significant improvement in disease activity as measured by the Crohn's disease activity index (metronidazole 20 mg/kg, 97 units; metronidazole 10 mg/kg, 67 units; placebo -1 unit, p = 0.002) and serum orosomucoid (metronidazole 20 mg/kg/day, 49; 10 mg/kg/day, 38; placebo, -9, p = 0.001)) were detected [16].

Biological context of ORM1

• The simultaneous expression could be explained in terms of an additional duplicated ORM1 locus haplotype, ORM1*5.2, whose average frequency was .016 in two Japanese populations [17].
• In comparison to healthy individuals from the same geographical area [6] the ORM1 S phenotypes are significantly more frequent in carcinoma patients [18].
• However, there also exists a genetic (protein-related) polymorphism coded by the ORM1 and ORM2 loci on chromosome 9 [5, 6] [18].
• Genetic polymorphism of orosomucoid (ORM1 and ORM2) in Lombardy (Italy) [19].
• Influence of the ORM1 phenotypes on serum unbound concentration and protein binding of quinidine [20].

Anatomical context of ORM1

• Using Hep3B hepatoma cells as a model system for the in vitro study of the acute phase reaction, we show that only AGP-A is strongly induced by treatment with culture medium of LPS stimulated monocytes [21].
• Local immunological reactions might influence the structure of alpha1-acid glycoprotein (AGP, orosomucoid) leading to a pathological condition in e.g. the thyroid [22].
• The influence of alpha1-acid glycoprotein (orosomucoid) and its glycoforms on the function of human thyrocytes and CHO cells transfected with the human TSH receptor [22].
• A probable mechanism may be that the ORM1 and C3 molecules modify the immune response by interacting with the lymphoid cell surface [12].
• The transition from one stage to another in the spermatogenic cycle is marked with an appearance of a receptor for the Concanavalin A (Con A) non-reactive glycoform AGP-A in the cytoplasm of spermatocytes, young spermatids and Sertoli cells [23].

Associations of ORM1 with chemical compounds

• In this study a modified isoelectric focusing, in which glycerin was omitted from gels, was used to differentiate a new variant ORM1 5 from ORM2 3 [17].
• ORM1 phenotyping by isoelectric focusing in agarose or polyacrylamide gel combined with either print immunofixation or enzyme-linked immunoblotting is described, and population and family data from Denmark and Southern Germany are given [24].
• The functional heterogeneity of ORM1 could be responsible for the differences in plasma binding of quinidine [20].
• Four of the seven systems (F13A, ORM1, AHSG, C6) have not been studied previously in sub-Saharan Africa, and one system (C7) has never been examined in any population of African ancestry [25].
• The variant allele originating from ORMi*S was characterized by a G-to-A transition, resulting in an amino acid change from valine to methionine, which is also detected in ORM1 F2, a form that is common in Europeans [26].

Physical interactions of ORM1

• Equine haptoglobin (Hp) and haptoglobin-haemoglobin complex (Hp-Hb) are metabolised in the hen parenchymal cells of the liver in which endocytosis was inhibited by agalacto-orosomucoid (AGOR) or native orosomucoid (OR) [27].

Other interactions of ORM1

• Orosomucoid and haptoglobin types in patients with sarcoidosis [1].
• Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in a Philippine population [28].
• These results, and comparison with other informative data, map the locus for AK-1 to 9q32 and that for ORM1 to region 9q31-q32 [29].
• At the F13A and ORM1 loci, Senegalese have allele frequencies similar to those reported for American blacks [25].
• 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 [30].

Analytical, diagnostic and therapeutic context of ORM1

• Using a pancolonic perfusion technique in 10 healthy volunteers (six females, four males, mean age 24 years), concentrations and outputs of Alb, immunoglobulins, SC, Oro, Transf and alpha 2-M were measured in the rectal effluents by immunoradiometric assay [31].
• Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant [32].
• In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin [32].
• Urinary beta 2-microglobulin, orosomucoid, albumin, transferrin and IgG were measured by enzyme-linked immunosorbent assays (ELISA) [33].
• The program comprised agar gel electrophoresis, total protein and albumin determination, and immunochemical determination of antitrypsin, orosomucoid, haptoglobin, IgR, and IgA [34].

References