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The secretor gene encodes for enzymes (glycosyltransferases), which become activein mucin-secreting cells like goblet and mucous cells of mucous membranes and different glands, resulting in the secretion of the corresponding blood group antigens in the body fluids [8].
In 1930 Putkonen noted that a person could be either secretor or non-secretor with respect to his genetic ability to secrete ABH blood group substances in secretions.2 It is now known that ABH blood group antigens (A B and H) are found on red blood cells lymphocytes platelets tissue cells body fluids (except CSF) and in secretions.34 Basic differences between secretors and non-secretors are qualitative and quantitative components of their saliva mucus and other body secretions.5ABH secretions are controlled by fucosyletransferase 2 (FUT2) secretor gene located on the short arm of chromosome number 19 in the form of two alleles denoted as Se" and se".
Two independent genes determine the Lewis phenotype; the Lewis gene (Le and le), and the secretor gene (Se and se; Fig.
Recently, the Lewis gene (FUT3) and the secretor gene (FUT2) were cloned (2, 3), and several silent alleles that cause the Lewis-negative (4-9) and the nonsecretor (1015) phenotypes, respectively, were identified.
As expected, individuals who were heterozygous mutated in the secretor gene (genotype groups 3 and 4) had higher concentrations of CA 19-9 in serum than individuals who were homozygous wild type (genotype groups 5 and 6; borderline significant for individuals who were homozygous wild type in the Lewis gene: P = 0.08 and 0.01).
Secretor gene inactivation by a novel single missense mutation A358T in Japanese nonsecretor individuals.
Lewis and secretor gene dosages affect CA 19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients.
Median, n kilounits/L All individuals 497 (b) 4.1 Women 118 5.2 Men 379 (b) 3.6 Genotype groups Lewis gene Secretor gene 1 Le/Le se/se 51 14.4 2 Le/le se/se 39 12.2 3 Le/Le Se/se 113 4.7 4 Le/le Se/se 91 3.7 5 Le/Le Se/Se 86 3.7 Le/le Se/Se 77 3.0 Upper reference Range, limit (a) kilounits/L kilounits/L [CV.sub.G], % All individuals <2.5-66.5 28.7 102.2 Women <2.5-47.2 30.2 94.2 Men <2.5-66.5 23.0 106.9 Genotype groups 1 2.9-61.2 50.6 69.4 2 2.6-30.0 30.0 45.9 3 <2.5-27.2 17.7 68.8 4 <2.5-12.1 11.0 48.2 5 <2.5-28.7 27.6 93.1 <2.5-10.2 7.9 42.9 (a) Upper reference limit is nonparametrically calculated 0.975 fractile.
The recent cloning of the secretor gene (FUT2) and the identification of enzyme-inactivating mutations and gene fusion [25-30] may even make it possible to classify the secretors as homozygous wild-type and heterozygous at the FUT2 locus, once the geographical distribution of inactivating mutations has been documented.
The synthesis of Ca 19-9 is complex because there are three genes involved: the secretor gene, the gene encoding the sialyltransferase, and the Lewis gene.
ABO, Le, and secretor genes control the enzyme glycosyltransferase.
The dosage of the Lewis gene [fucosyltransferase 3 (galactoside 3(4)-L-fucosyltransferase, Lewis blood group)] increases the amount of CA 19-9, whereas the dosage of secretor genes decreases it (6).