Histo-blood group ABO system transferase is an
enzyme with
glycosyltransferase activity, which is encoded by the ''ABO''
gene in humans.
It is ubiquitously expressed in many tissues and cell types. ABO determines the
ABO blood group
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 43 different blood type (or group) classification system ...
of an individual by modifying the oligosaccharides on cell surface glycoproteins. Variations in the sequence of the protein between individuals determine the type of modification and the blood group. The ''ABO'' gene also contains one of 27
SNPs associated with increased risk of
coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
.
Alleles
The ''ABO'' gene resides on chromosome 9 at the band 9q34.2 and contains 7
exons
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
.
The ''ABO'' locus encodes three
alleles, that is, 3 variants of the same gene. One allele is derived from each parent.
The A allele produces α-1,3-N-acetylgalactosamine transferase (A-transferase), which catalyzes the transfer of GalNAc
residues from the UDP-GalNAc donor nucleotide to the Gal residues of the acceptor
H antigen, converting the H antigen into
A antigen
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 43 different blood type (or group) classification system ...
in A and AB individuals.
The B allele encodes α-1,3-galactosyl transferase (B-transferase), which catalyzes the transfer of Gal residues from the
UDP-Gal donor nucleotide to the Gal residues of the acceptor H antigen, converting the H antigen into
B antigen
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 43 different blood type (or group) classification system ...
in B and AB individuals. Remarkably, the difference between the A and B glycosyltransferase enzymes is only four
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
.
The O allele lacks both enzymatic activities because of the frameshift caused by a deletion of guanine-258 in the gene which corresponds to a region near the
N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
of the protein.
This results in a
frameshift
Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process c ...
and thus of a truncated protein of only 117
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
.
The truncated protein is unable to modify
oligosaccharides which end in
fucose linked to
galactose. Thus no A or B antigen is found in O individuals. This sugar combination is termed the
H antigen. These antigens play an important role in the match of
blood transfusion and
organ transplantation.
Other minor alleles have been found for this gene.
Common alleles
There are six common
alleles in individuals of European descent. Nearly every living human's
phenotype for the ABO gene is some combination of just these six alleles:
*A
**''A101'' (A1)
**''A201'' (A2)
*B
**''B101'' (B1)
*O
**''O01'' (O1)
**''O02'' (O1v)
**''O03'' (O2)
Many rare variants of these alleles have been found in human populations around the world.
Clinical significance
In human cells, the ABO alleles and their encoded glycosyltransferases have been described in several oncologic conditions. Using anti-GTA/GTB monoclonal antibodies, it was demonstrated that a loss of these enzymes was correlated to malignant bladder and oral epithelia. Furthermore, the expression of ABO blood group antigens in normal human tissues is dependent upon the type of differentiation of the epithelium. In most human carcinomas, including oral carcinoma, a significant event as part of the underlying mechanism is decreased expression of the A and B antigens.
Several studies have observed that a relative down-regulation of GTA and GTB occurs in oral carcinomas in association with tumor development.
More recently, a genome wide association study (GWAS) has identified variants in the ABO locus associated with susceptibility to
pancreatic cancer
Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...
.
Clinical marker
A multi-locus genetic risk score study based on a combination of 27
loci
Locus (plural loci) is Latin for "place". It may refer to:
Entertainment
* Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front
* ''Locus'' (magazine), science fiction and fantasy magazine
** '' Locus Award ...
, including the ABO gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).
References
Further reading
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See also
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RHD (gene)
Rh blood group, D antigen also known as Rh polypeptide 1 (RhPI) or cluster of differentiation 240D (CD240D) is a protein that in humans is encoded by the ''RHD'' gene.
The RHD gene codes for the RhD erythrocyte membrane protein that is the Rh fa ...
External links
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{{DEFAULTSORT:Abo