Lewis enzyme (α1–3/4 fucosyltransferase) polymorphisms do not explain the Lewis phenotype in the gastric mucosa of a Portuguese population

Serpa, Jacinta; Almeida, Raquel; Oliveíra, Carla; Santos-Silva, Filipe; Silva, Elisabete; Reis, Celso A.; Pendu, Jacques Le; Oliveira, Graça; Ribeiro, Letícia; David, Leonor

doi:10.1007/s10038-003-0007-5

Cited by 16 publications

(11 citation statements)

References 34 publications

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“…The Lewis phenotyping and FUT3 genotyping revealed not only that Lewis status (positive vs. negative) is not a predictive marker for NoV infection, an observation consistent with another report [Larsson et al, 2006] but also that the Le aÀbÀ individuals can be infected with both GI and GII viruses, an observation not made previously (Table I). Furthermore, the 25% Lewis negative (Le aÀbÀ ) individuals observed in this study is significantly higher than the 5.7% observed in Scandinavia or the 10% observed in Portugal and Spain [Torrado et al, 1997;Serpa et al, 2003;Larsson et al, 2006]. However, the frequency of Lewis-negative individuals in Nicaragua is similar to Colombia (22%) [Torrado et al, 1997] and can reach up to 40% in isolated black communities in Brazil [Corvelo et al, 2002].…”

Section: Discussionmentioning

confidence: 46%

Genetic susceptibility to symptomatic norovirus infection in Nicaragua

Bucardo

Kindberg

Paniagua

et al. 2009

Journal of Medical Virology

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Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.

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Section: Discussionmentioning

confidence: 46%

Genetic susceptibility to symptomatic norovirus infection in Nicaragua

Bucardo

Kindberg

Paniagua

et al. 2009

Journal of Medical Virology

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“…To our knowledge, this is the first report of chronic calicivirus shedding and RNA evolution, and the results support the hypothesis of an immune-response-driven mechanism for calicivirus RNA evolution. We also provide host genetic information that support the hypothesis of specific histo-blood group antigens and calicivirus resistance (6,13,23).…”

mentioning

confidence: 56%

Evolution of Human Calicivirus RNA In Vivo:Accumulation of Mutations in the Protruding P2 Domain of the CapsidLeads to Structural Changes and Possibly a NewPhenotype

Nilsson

Hedlund²,

Thorhagen³

et al. 2003

J Virol

184

158

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In the present study we report on evolution of calicivirus RNA from a patient with chronic diarrhea (i.e., lasting >2 years) and viral shedding. Partial sequencing of open reading frame 1 (ORF1) from 12 consecutive isolates revealed shedding of a genogroup II virus with relatively few nucleotide changes during a 1-year period. The entire capsid gene (ORF2) was also sequenced from the same isolates and found to contain 1,647 nucleotides encoding a protein of 548 amino acids with similarities to the Arg320 and Mx strains. Comparative sequence analysis of ORF2 revealed 32 amino acid changes during the year. It was notable that the vast majority of the cumulative amino acid changes (8 of 11) appeared within residues 279 to 405 located within the hypervariable domain (P2) of the capsid protein and hence were subject to immune pressure. An interesting and novel observation was that the accumulated amino acid changes in the P2 domain resulted in predicted structural changes, including disappearance of a helix structure, and thus a possible emergence of a new phenotype. FUT2 gene polymorphism characterization revealed that the patient is heterozygous at nucleotide 428 and thus Secretor ؉ , a finding in accordance with the hypothesis of FUT2 gene polymorphism and calicivirus susceptibility. To our knowledge, this is the first report of RNA evolution of calicivirus in a single individual, and our data suggest an immunity-driven mechanism for viral evolution. We also report on chronic virus excretion, immunoglobulin treatment, and modification of clinical symptoms; our observations from these studies, together with the FUT2 gene characterization, may lead to a better understanding of calicivirus pathogenesis.Acute diarrheal diseases are common in humans and are associated with significant morbidity worldwide and substantial mortality in developing countries. In recent years, caliciviruses have emerged as an important cause of gastroenteritis in all age groups and are now recognized as the main cause of gastroenteritis in nursing homes and hospitals (3,8,12,14,15,27).Caliciviruses are classified into four genera: norovirus, sapovirus, vesivirus, and logovirus. Human caliciviruses are found within the norovirus and sapovirus genera, which contain a wide range of genetically distinct strains. The sequence heterogeneity of these strains may be a result of the high mutation rate caused by the lack of proofreading of the polymerase. However, the sequence variation has also raised the possibility that calicivirus RNA undergoes constant genetic drift through immune-response-driven mechanisms, leading to the emergence of new strains. However, at present there is no information on human calicivirus mutation rates over time, nor has the importance of immune-response-driven mutations been reported.The clinical features of a calicivirus infection includes an incubation period of 12 to 48 h characterized by acute onset of nausea, vomiting, abdominal cramps and diarrhea that generally lasts for about 48 h. Recent studies have shown, howe...

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“…For example, the Secretor ( FUT2 ) and Le ( FUT3 ) genes control the expression of enzymes in the synthetic pathway that governs expression of critical antigenic saccharide residues and, thus, an individual’s presentation of Le blood group structures (28). Accordingly, depending on their genetic makeup, many populations have high background concentrations of these epitopes present as normal components of serum and other secreted glycoproteins (29, 30). Several groups have proposed including analysis of an individual’s Secretor and Le blood group status to improve the diagnostic sensitivity and specificity of serum CA19-9 tests (28, 31).…”

Section: Clinical Tests Based On Cancer-related Changes In Glycosylationmentioning

confidence: 99%

Sweetening the Pot: Adding Glycosylation to the Biomarker Discovery Equation

et al. 2010

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Background: Cancer has profound effects on gene expression, including a cell’s glycosylation machinery. Thus, tumors produce glycoproteins that carry oligosaccharides with structures that are markedly different from the same protein produced by a normal cell. A single protein can have many glycosylation sites that greatly amplify the signals they generate compared with their protein backbones. Content: In this article, we survey clinical tests that target carbohydrate modifications for diagnosing and treating cancer. We present the biological relevance of glycosylation to disease progression by highlighting the role these structures play in adhesion, signaling, and metastasis and then address current methodological approaches to biomarker discovery that capitalize on selectively capturing tumor-associated glycoforms to enrich and identify disease-related candidate analytes. Finally, we discuss emerging technologies—multiple reaction monitoring and lectin-antibody arrays—as potential tools for biomarker validation studies in pursuit of clinically useful tests. Summary: The future of carbohydrate-based biomarker studies has arrived. At all stages, from discovery through verification and deployment into clinics, glycosylation should be considered a primary readout or a way of increasing the sensitivity and specificity of protein-based analyses.

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Lewis enzyme (α1–3/4 fucosyltransferase) polymorphisms do not explain the Lewis phenotype in the gastric mucosa of a Portuguese population

Cited by 16 publications

References 34 publications

Genetic susceptibility to symptomatic norovirus infection in Nicaragua

Genetic susceptibility to symptomatic norovirus infection in Nicaragua

Evolution of Human Calicivirus RNA In Vivo:Accumulation of Mutations in the Protruding P2 Domain of the CapsidLeads to Structural Changes and Possibly a NewPhenotype

Sweetening the Pot: Adding Glycosylation to the Biomarker Discovery Equation

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