Orosomucoid 1

Alternative Names

ORM1
ORM
Glycoprotein, Alpha-1-Acid, of Serum
Alpha-1-Acid Glycoprotein
Alpha-1-AGP
AGP1

Associated Diseases

Orosomucoid 2

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OMIM Number

138600

Gene Map Locus

9q34.1-q34.3

Description

ORM1 gene encodes one of the two forms of a plasma protein called orosomucoid (ORM). The plasma ORM proteins present as a mixture of ORM1 and ORM2 proteins in a molar ratio of 3:1, respectively. ORM protein is a member of the lipocalin family and is one of the most important glycoprotein components of blood plasma. ORM protein is a relatively abundant plasma protein with a concentration of 2.5 mg/ml in healthy normal individuals. This concentration is known to rise dramatically in response to acute infection, inflammation, surgery, cancer, and other stimuli. This phenomenon, known as the acute phase reaction, is common to all mammals. The proteins participating in it are known as acute phase reactants and ORM protein is a major acute-phase reactive plasma protein. ORM is also considered a binding protein for certain drugs in plasma. Additionally, it is an immunomodulatory protein with the ability to down regulate complement activation, along with various phagocytic functions and T-cell-mediated activities.

Molecular Genetics

ORM1 gene is located on the long arm of chromosome 9 at 9q34.1-q34.3. It consists of six exons and five introns. ORM protein is synthesized in the liver and secreted in the blood. It is composed of a single polypeptide chain of 183 amino acids with 45% carbohydrate content and 12% sialic acid residues.

ORM1 is highly polymorphic. The three common ORM1 alleles result from A to G transitions at the nucleotide positions 1721 in exon 1, amino acid 20 (Gln20Arg), along with nucleotide position 3615 in exon 5, amino acid 156 (Val156Met), of the ORM1 gene: ORM1*F1 is characterized by CAG (Gln) and GTG (Val), ORM1*F2, by CAG (Gln) and ATG (Met), and ORM1*S, by CGG (Arg) and GTG (Val). The ORM1*F1 allele increases in frequency from west to east, that is, from Europe through the Middle East, India, Nepal, and Sri Lanka to East Asia, and there is a corresponding reverse trend in frequencies of the other common allele ORM1*S. The relatively rare allele ORM1*F2 is polymorphic in Europe and the Middle East but is absent in most East Asian populations (Japan, Taiwan, Thailand, and others). East Asian populations have a different polymorphic allele. The duplicate allele, ORM1*dF1,S, occurs in the Japanese population at an appreciable frequency (up to 16%).

There are some reports indicating that these polymorphisms are clinically significant. An association between ORM1*F and ORM1*S with several neoplastic disorders, including breast and lung cancers, and immunologically mediated diseases, such as sarcoidosis, has been reported. In addition, the bioavailability of basic or neutral drugs, and the serum concentration of hydrophobic molecules, such as some lipids and steroids, appears to be affected by specific ORM1 alleles.

Epidemiology in the Arab World

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Other Reports

Egypt

Sebetan et al. (1997) carried out a study to investigate the genetic variants of the human plasma orosomucoid ORM1 and ORM2 gene loci in Egyptians. In this study, 271 plasma samples from unrelated healthy blood donors were collected and used within a few days of collection. Isoelectric focusing was used for phenotyping all samples. Also, Sebetan et al. (1997) studied the ORM1 locus in the Qatari and Sudanese populations. In the three populations, the ORM1 locus showed 18 different phenotypes that are determined by 10 ORM1 alleles: ORM1*F1, ORM1*S, ORM1*dF1S, ORM1*F2, ORM1*A3, ORM1*B4, ORM1*B10, ORM1*C3, ORM1*C7 and a new allele designated ORM1*B13. Family studies of this new allele are in accordance with co-dominant autosomal inheritance. Sebetan et al. (1997) found seven ORM1 alleles in Egyptians which are in decreasing order: ORM1*F1, ORM1*S, ORM1*dF1S, ORM1*F2, ORM1*B4, ORM1*B13, ORM1*C3. The most common phenotype in Egyptians is F1.S (determined by two ORM1 (F1/S and dF1S/dF1S) genotypes) of the ORM1 combined with M phenotype of the ORM2. Out of the 271, 119 had this phenotype. The phenotype F1 and S of the ORM1 each combined with M phenotype of the ORM2 was found in 90 and 35 Egyptians, respectively.

Libya

Sebetan and Sagisaka (1988) characterized the genetic polymorphisms of orosomucoid ORM1 in Libyans and indicated the occurrence of the ORM1*2.1 haplotype. No further details could be obtained on this subject.

Qatar

Sebetan et al. (1997) carried out a study to investigate the genetic variants of the human plasma orosomucoid ORM1 and ORM2 gene loci in Qataris. In this study, 400 plasma samples from unrelated healthy blood donors were collected and used within a few days of collection. Sebetan et al. (1997) found six ORM1 alleles in Qataris that are in decreasing order: ORM1*F1, ORM1*S, ORM1*dF1S, ORM1*F2, ORM1*A3, and ORM1*B10. The most common phenotype in the Qatri population is F1.S (determined by two ORM1 (F1/S and dF1S/dF1S) genotypes) of the ORM1 combined with M phenotype of the ORM2. Out of the 400 subjects analyzed, 177 had this phenotype. The phenotype F1 and S of the ORM1 each combined with M phenotype of the ORM2 was found in 139 and 59 Qataris, respectively [See also: Egypt > Sebetan et al., 1997].

Sudan

Sebetan et al. (1997) carried out a study to investigate the genetic variants of the human plasma orosomucoid ORM1 and ORM2 gene loci in Sudanese. In this study, 195 plasma samples from unrelated healthy blood donors were collected and used within a few days of collection. Sebetan et al. (1997) found seven ORM1 alleles in Sudanese people that are in decreasing order: ORM1*F1, ORM1*S, ORM1*dF1S, ORM1*F2, ORM1*B10, ORM1*B13, and ORM1*C7. The most common phenotype occurring in Sudanese is F1.S (determined by two ORM1 (F1/S and dF1S/dF1S) genotypes) of the ORM1 combined with M phenotype of the ORM2. Out of the 195 subjects analyzed, 82 had this phenotype. The phenotype F1 and S of the ORM1 each combined with M phenotype of the ORM2 was found in 55 and 72 Sudanese, respectively [See also: Egypt > Sebetan et al., 1997].

External Links

http://www.genecards.org/cgi-bin/carddisp.pl?gene=ORM1

Contributors

Pratibha Nair: 10.05.2011
Ghazi O. Tadmouri: 05.05.2009
Tasneem Obeid: 29.06.2008

Edit History

Pratibha Nair: 14.05.2015
Pratibha Nair: 10.05.2011
Tasneem Obeid: 07.05.2009