Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant

Autor: Frédérique Bourgaud, Nadir Mrabet, Isabelle Gross, Thomas Josse, Philippe Gérard, Cyril Besseau, Laurent Peyrin-Biroulet, Jean Devignes, Abderrahim Oussalah, François Feillet, Jean-Louis Guéant, Elise Jeannesson, Céline Chéry, Jean-Noël Freund, Alain Hehn, Jean-Marc Alberto, Rosa Maria Guéant-Rodriguez
Přispěvatelé: Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Laboratoire Agronomie et Environnement (LAE), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), De l'homéostasie tissulaire au cancer et à l'inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Metabolic Unit, University Children's Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), French National Agency for Research (ANR Nutrivigene), Regions of Lorraine (France)
Rok vydání: 2013
Předmět:
Adult
Intrinsic Factor
Male
Heterozygote
medicine.medical_specialty
FUT2
Population
[SDV.SA.AGRO]Life Sciences [q-bio]/Agricultural sciences/Agronomy
Genome-wide association study
Biology
Gastric intrinsic factor
Biochemistry
Cobalamin
Helicobacter Infections
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Anemia
Pernicious
Genotype
medicine
Humans
Vitamin B12
Allele
education
030304 developmental biology
0303 health sciences
education.field_of_study
Intrinsic factor
nutritional and metabolic diseases
General Medicine
Fucosyltransferases
3. Good health
Vitamin B 12
Endocrinology
chemistry
Mutation
Immunology
Female
Inherited intrinsic factor deficiency
Gastritis
medicine.symptom
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: Biochimie
Biochimie, Elsevier, 2013, 95 (5), pp.995-1001. ⟨10.1016/j.biochi.2013.01.022⟩
ISSN: 0300-9084
DOI: 10.1016/j.biochi.2013.01.022
Popis: International audience; Several genome-wide association studies (GWAS) have identified a strong association between serum vitamin B12 and fucosyltransferase 2 (FUT2), a gene associated with susceptibility to Helicobacter pylori infection. Hazra et al. conducted a meta-analysis of three GWAS and found three additional loci in MUT, CUBN and TCN1. Other GWAS conducted in Italy and China confirmed the association for FUT2 gene. Alpha-2-fucosyltransferase (FUT2) catalyzes fucose addition to form H-type antigens in exocrine secretions. FUT2 non-secretor variant produces no secretion of H-type antigens and is associated with high-plasma vitamin B12 levels. This association was explained by the influence of FUT2 on H. pylori, which is a risk factor of gastritis, a main cause of vitamin B12 impaired absorption. However, we recently showed that H. pylori serology had no influence on FUT2 association with vitamin B12, in a large sample population, suggesting the involvement of an alternative mechanism. GIF is another gene associated with plasma levels of vitamin B12 and gastric intrinsic factor (GIF) is a fucosylated protein needed for B12 absorption. Inherited GIF deficiency produces B12 deficiency unrelated with gastritis. We report 2 families with heterozygous GIF mutation, 290T>C, M97T, with decreased binding affinity of GIF for vitamin B12 and one family with heterozygous GIF mutation 435\₄37delGAA, K145_N146delinsN and no B12 binding activity of mutated GIF. All cases with vitamin B12 deficit carried the FUT2 rs601338 secretor variant. Ulex europeus binding to GIF was influenced by FUT2 genotypes and GIF concentration was lower, in gastric juice from control subjects with the secretor genotype. GIF290C allele was reported in 5 European cases and no Africans among 1282 ambulatory subjects and was associated with low plasma vitamin B12 and anaemia in the single case bearing the FUT2 secretor variant. We concluded that FUT2 secretor variant worsens B12 status in cases with heterozygous GIF mutations by impairing GIF secretion, independently from H. pylori-related gastritis.
Databáze: OpenAIRE
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