Genetic study of orosomucoid by isoelectric focusing and immunoprinting in patients with carcinoma

Abstract

The carbohydrate moiety of the orosomucoid (ORM) molecule shows microheterogeneity [1] and the pteridine-containing variant seems to be tumor-specific [2-4]. However, there also exists a genetic (protein-related) polymorphism coded by the ORM1 and ORM2 loci on chromosome 9 [5, 6]. To investigate the relationship between ORM1 gene products and the development of carcinoma, we analyzed the ORM1 phenotypes of desialated sera from 125 patients with carcinoma. The allele frequencies were estimated for ORM1*F1 0.556, ORM1*F2 0.012 and ORM1*S 0.432. In comparison to healthy individuals from the same geographical area [6] the ORM1 S phenotypes are significantly more frequent in carcinoma patients. The patients' sera frequently showed additional ORM-positive proteins which focused slightly cathodically to the ORM 2 A band. These proteins may represent posttranslational modifications of the ORM1*S allele product. Whether these modifications are tumor-specific and related to the carbohydrate moiety of the molecule must be confirmed in further studies.

Association between Orosomucoid Types and Cancer

“…The frequency of the ORM1 2 type was increased among the cancer patients with a relative risk (RR) of 1.56 [95% confidence interval (Cl) = 1.16-2.09], This is in good agreement with the results of Mittermiiller and Weidinger [16], where the RR was 1.52 (95%CI = 1.13-2.04). Thus, individuals with the ORM 1 2 type appear to have on average a 50% higher risk for different types of carcinomas.…”

“…The frequency in the control sample (0.389) is similar to that in other European populations and, e.g., very close to the frequency (0.386) found in Denmark [19]. The obser vations in this study and in the previous study by Mittermiiller and Weidinger [16] contrast with the Findings of lower RRs for ORM 1 2 individuals in psoriasis, sarcoid osis and allergic contact dermatitis [13][14][15], All these associations between ORM 1 types and disease could be explained by the hypothesis that the ORM1 2 variant is more immunosuppressive than the ORM1 1 variant. Thus the ORM 1 2 type and to some extent the ORM 1 2-1 type would act as a blocking agent protecting the tumor cells against immunological attack more than the ORM 1 1 type.…”

“…The ORM 1 1 type has been found to be associated with psoria sis [13], sarcoidosis [14] and allergic contact dermatitis [15], Altogether, the results suggested that the ORM1 1 type may be a contributory determinant in multifactorial immunogenetic disorders by influencing the progression and clinical course rather than the onset of these disor ders. In contrast to the disease associations with ORM 1 1 mentioned above, Mittermiiller and Weidinger [16] re ported an increased frequency of the ORM1 2 type in patients with different types of carcinomas. In the present report, data confirming the association between the ORM 1 2 type and cancer are presented.…”

CIEF with hydrodynamic and chemical mobilization for the separation of forms of α‐1‐acid glycoprotein

“…In this regard, slab gel IEF has been used to demonstrate that the expression of genetic variants of AGP may change with the type of cancer [4] and that some phenotypes are significantly more frequent in carcinoma patients in comparison with healthy individuals [11]. This technique has also been used to study changes in the forms of AGP in acute inflammation stages [1].…”

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

“…Several groups have pointed out the possible clinical significance of the mentioned ORM1 polymorphisms (Mittermüller and Weidinger, 1992;Fan et al, 1995a,b;Duche et al, 2000;Lee et al, 2001;Hashimoto et al, 2004). According to previous observations, the A/G (Gln20Arg) variants of exon 1 of ORM1 have been found to be associated with sarcoidosis (A allele), and with lung and breast cancer (G allele) (Fan et al, 1995b).…”