Lewis enzyme (α1–3/4 fucosyltransferase) polymorphisms do not explain the Lewis phenotype in the gastric mucosa of a Portuguese population (original) (raw)
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Journal of Human Genetics, 2003
The human a-1,3/4 fucosyltransferase III (FucT III) catalyses the synthesis of Lewis antigens including Le b antigen which is a ligand for Helicobacter pylori adhesion. Several polymorphisms have been described in the FUT3 gene affecting both the transmembrane and catalytic domains, some of which affect the enzyme activity. The aim of the present work was to study the Lewis gene polymorphisms in a Caucasian Portuguese population, with a high rate of H. pylori infection, and to evaluate the implications of mutant enzymes in Le b expression in the gastric mucosa. We studied 460 asymptomatic or dyspeptic individuals from northern Portugal. Screening for Lewis gene polymorphisms was performed by SSCP and direct sequencing. Lewis phenotype in gastric mucosa was determined by immunohistochemistry. In 47 individuals with a Lewis negative blood group, we found FUT3 gene polymorphisms that were previously described in other populations: 59T>G, 202T>C, 314C>T, 508G>A and 1067T>A. Among the 47 Lewis negative individuals in blood, only nine were also negative in gastric mucosa, suggesting the existence of another a 1-4 fucosyltransferase that is responsible for Le a and Le b synthesis in gastric mucosa.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2001
Helicobacter pylori attach to the gastric mucosa with adhesin, which binds to Lewis b (Le(b)) or H type I carbohydrate structures. The Secretor (Se) gene and Lewis (Le) gene are involved in type I Le antigen synthesis. The present study was performed to investigate the possibility that Se and Le gene polymorphisms alter the risk of H. pylori infection. Two hundred thirty-nine participants were genotyped for Se and Le and tested for the presence of anti-H. pylori IgG antibodies. Using the normal gastric mucosa from 60 gastric cancer patients, we assessed immunohistochemically whether type I Le antigen expression depended on the Se and Le genotypes. The H. pylori infection rate was positively associated with the number of Se alleles (se/se group, 45.1%; Se/se group, 64.6%; and Se/Se group, 73.3%) and negatively associated with the number of Le alleles (le/le group, 76.4%; Le/le group, 68.3%; and Le/Le group, 55.6%). When the subjects were classified into three groups [low risk, (se/se...
ASSOCIATION OF HELICOBACTER PYLORI WITH THE LEWIS ANTIGEN: A LITERATURE REVIEW (Atena Editora)
ASSOCIATION OF HELICOBACTER PYLORI WITH THE LEWIS ANTIGEN: A LITERATURE REVIEW (Atena Editora), 2023
Since the 90s, several studies have presented the probable relationship between antigens of the ABO-Lewis system and susceptibility to infections, as they end up serving as receptors or co-receptors for these microorganisms. This literary review study aimed to demonstrate the correlation between the pathogenesis of infection by Helicobacter pylori and the Lewis blood system, in order to spread knowledge of the importance of blood phenotypes to health professionals. Data collection was carried out using the PubMed and SciELO reference bases over a period of 20 years (2002 - 2022) with the terms "Blood type", "Lewis system", "ABO system'', "H. Pylori", “Helicobacter pylori.” Helicobacter pylori binds to the antigen Lewis b (Le b), rich in fucose and expressed on the surface of gastric epithelial cells. Furthermore, Le b has high affinity for BabA adhesins, one of the virulence factors of this genus of bacteria that infect humans and promote chronic inflammation and/or other gastric diseases. Since infection by this microorganism is characterized by chronicity, knowledge of its pathogenesis and correlation with all types of risk factors is an important prevention mechanism.
Journal of Biological Chemistry, 1997
The Lewis ␣(1,3/1,4)-fucosyltransferase, Fuc-TIII, encoded by the FUT3 gene is responsible for the final synthesis of Le a and Le b antigens. Various point mutations have been described explaining the Lewis negative phenotype, Le(a؊b؊), on erythrocytes and secretions. Two of these, T202C and C314T originally described in a Swedish population, have not been found as single isolated point mutations so far. To define the relative contribution of each of these two mutations to the Lewis negative phenotype, we cloned and made chimeric FUT3 constructs separating the T202C mutation responsible for the amino acid change Trp 68 3 Arg, from the C314T mutation leading to the Thr 105 3 Met shift. COS-7 cells were transfected and the expression of Fuc-TIII enzyme activity and the presence of Lewis antigens were determined. There was no decrease in enzyme activity nor of immunofluorescence staining on cells transfected with the construct containing the isolated C314T mutation compared with cells transfected with a wild type FUT3 allele control. No enzyme activity nor immunoreactivity for Lewis antigens was detected in FUT3 constructs containing both mutations in combination. The T202C mutation alone decreased the enzyme activity to less than 1% of the activity of the wild type FUT3 allele. These results demonstrate, that the Trp 68 3 Arg substitution in human Fuc-TIII is the capital amino acid change responsible for the appearance of the Le(a؊b؊) phenotype on human erythrocytes in individuals homozygous for both the T202C and C314T mutations. 1 The abbreviations used are: Le or Lewis enzyme, FUT3-encoded ␣(1,3/1,4)-fucosyltransferase; H enzyme (EC 2.4.1.69), FUT1-encoded ␣(1,2)-fucosyltransferase; Se or secretor enzyme, FUT2-encoded ␣(1,2)fucosyltransferase; Fuc-TIII (EC 2.4.1.65), Fuc-TIV, or myeloid enzyme, FUT4-encoded ␣(1,3)-fucosyltransferase; Fuc-TV, FUT5-encoded ␣(1,3/ 1,4)-fucosyltransferase; Fuc-TVI (EC 2.4.1.152) or plasma enzyme, FUT6-encoded ␣(1,3)-fucosyltransferase; Fuc-TVII or leukocyte enzyme, FUT7-encoded ␣(1,3)-fucosyltransferase; PCR, polymerase chain reaction; bp, base pair.
The Journal of Infectious Diseases, 2001
There are no reports, to our knowledge, on the expression of Lewis (Le) antigens in Helicobacter pylori isolates from children. The aim of this study was to compare the expression of Le antigens by H. pylori isolates from children and from adults. Totals of 278 clones from 22 children with recurrent abdominal pain and 293 clones from 22 adults with ( ) or n p 10 without ( ) duodenal ulcer were studied. Expression of Le x and Le y antigens was de-n p 12 termined by ELISA, using monoclonal anti-Le antibodies. The Le phenotype of the patients was determined in gastric juice with a hemagglutination assay. Clones expressing Le x were more common in children than in adults (55.4% vs. 33.4%, respectively; ), and Le y P ! .001 was more common in adults than in children (81.6% vs. 66%, respectively; ). A trend P ! .01 analysis showed a significant decline in frequency of clones expressing Le x with age (P p ). In this community, expression of Le antigens differs in H. pylori isolates obtained from .021 children versus adults.
Journal of Biological Chemistry, 1997
The Lewis ␣(1,3/1,4)-fucosyltransferase, Fuc-TIII, encoded by the FUT3 gene is responsible for the final synthesis of Le a and Le b antigens. Various point mutations have been described explaining the Lewis negative phenotype, Le(a؊b؊), on erythrocytes and secretions. Two of these, T202C and C314T originally described in a Swedish population, have not been found as single isolated point mutations so far. To define the relative contribution of each of these two mutations to the Lewis negative phenotype, we cloned and made chimeric FUT3 constructs separating the T202C mutation responsible for the amino acid change Trp 68 3 Arg, from the C314T mutation leading to the Thr 105 3 Met shift. COS-7 cells were transfected and the expression of Fuc-TIII enzyme activity and the presence of Lewis antigens were determined. There was no decrease in enzyme activity nor of immunofluorescence staining on cells transfected with the construct containing the isolated C314T mutation compared with cells transfected with a wild type FUT3 allele control. No enzyme activity nor immunoreactivity for Lewis antigens was detected in FUT3 constructs containing both mutations in combination. The T202C mutation alone decreased the enzyme activity to less than 1% of the activity of the wild type FUT3 allele. These results demonstrate, that the Trp 68 3 Arg substitution in human Fuc-TIII is the capital amino acid change responsible for the appearance of the Le(a؊b؊) phenotype on human erythrocytes in individuals homozygous for both the T202C and C314T mutations. 1 The abbreviations used are: Le or Lewis enzyme, FUT3-encoded ␣(1,3/1,4)-fucosyltransferase; H enzyme (EC 2.4.1.69), FUT1-encoded ␣(1,2)-fucosyltransferase; Se or secretor enzyme, FUT2-encoded ␣(1,2)fucosyltransferase; Fuc-TIII (EC 2.4.1.65), Fuc-TIV, or myeloid enzyme, FUT4-encoded ␣(1,3)-fucosyltransferase; Fuc-TV, FUT5-encoded ␣(1,3/ 1,4)-fucosyltransferase; Fuc-TVI (EC 2.4.1.152) or plasma enzyme, FUT6-encoded ␣(1,3)-fucosyltransferase; Fuc-TVII or leukocyte enzyme, FUT7-encoded ␣(1,3)-fucosyltransferase; PCR, polymerase chain reaction; bp, base pair.
Journal of Biomedical Science, 2007
This study tested whether there were different expressions of gastric Lewis antigens between children and adults with Helicobacter pylori infection, and whether the difference was related to the infection outcome. About 68 dyspeptic children and 110 dyspeptic adults were enrolled to check H. pylori infection, its colonization density, and the related histology. Gastric Lewis antigens b (Le(b)), x (Le(x)), and sialyl-Lewis x (sialyl-Le(x)) were immunohistochemically stained and scored for the intensity. The H. pylori-infected adults, but not the children, had a lower Le(b) intensity over the antrum (p=0.019) but higher Le(b) intensity over the corpus (p=0.001) than the non-infected ones. Over the antrum, both the H. pylori-infected children and adults had a lower Le(x) and higher sialyl-Le(x) intensity than those non-infected ones (p<0.05). The H. pylori-infected adults had a higher bacterial density (p=0.004) and Le(b) intensity (p=0.016) over the corpus than the H. pylori-infected children. For the H. pylori-infected adults, but not children, the corpus had a higher Le(b) (p=0.038) and lower Le(x) (p=0.005) intensity than the antrum. Furthermore, the H. pylori-infected adults expressed a higher Le(b) and had a higher bacterial density than those with weak Le(b) (antrum, p<0.001; corpus, p=0.001). In conclusion, H. pylori infection is associated with the intensity change of Lewis antigen expressions in the stomach. The changes of gastric Lewis antigen expressions are different between adults and children with H. pylori infection, which may exert different H. pylori colonization over the corpus between adults and children.
Lewis blood genotypes of peptic ulcer and gastric cancer patients in Taiwan
2000
The Lewis b (Le b ) antigen has been implicated as a possible binding site for attachment of Helicobacter pylori (H pylori) to gastric mucosa. However, studies both supporting and denying this association have been reported in the literature. Differences in secretor (Se) genotype have been suggested as a possible reason for previous discrepancies. Therefore, we investigated the relationship between Le and Se genotypes and H pylori infection rates in people with peptic ulcer or gastric cancer.