Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families

Autor: Jacques Schmitz, Mathilde Di Filippo, Dominique Bonnefont-Rousselot, Sabrina Dumont, Latifa Ferkdadji, Catherine Boileau, Mathilde Varret, V. Boehm, Francisca Joly, Jean-Pierre Rabès, Laurent Abramowitz, Catherine Lenaerts, Marie-Elisabeth Samson-Bouma
Přispěvatelé: Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Robert Debré, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), CHU Necker - Enfants Malades [AP-HP], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CarMeN, laboratoire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Apolipoprotein B
Endocrinology
Diabetes and Metabolism
[SDV]Life Sciences [q-bio]
Liver steatosis
030204 cardiovascular system & hematology
Compound heterozygosity
Microsomal triglyceride transfer protein
chemistry.chemical_compound
0302 clinical medicine
030212 general & internal medicine
Child
Fat malabsorption
Sequence Deletion
Nutrition and Dietetics
biology
medicine.diagnostic_test
Postprandial
Middle Aged
Postprandial Period
Abetalipoproteinemia
Pedigree
3. Good health
[SDV] Life Sciences [q-bio]
Liver
Child
Preschool
Cardiology and Cardiovascular Medicine
Adult
Heterozygote
medicine.medical_specialty
Adolescent
Genotype
Young Adult
03 medical and health sciences
Malabsorption Syndromes
Internal medicine
Internal Medicine
medicine
Humans
Apolipoproteins B
Polymorphism
Genetic
Triglyceride
business.industry
Infant
Lipid Metabolism
medicine.disease
Genetic hypocholesterolemia
Endocrinology
chemistry
biology.protein
Liver function
Steatosis
Carrier Proteins
Liver function tests
business
Zdroj: Journal of clinical lipidology
Journal of clinical lipidology, Elsevier, 2019, 13 (1), pp.201-212. ⟨10.1016/j.jacl.2018.10.003⟩
Journal of clinical lipidology, 2019, 13 (1), pp.201-212. ⟨10.1016/j.jacl.2018.10.003⟩
ISSN: 1933-2874
DOI: 10.1016/j.jacl.2018.10.003⟩
Popis: International audience; BACKGROUND: Abetalipoproteinemia, a recessive disease resulting from deleterious variants in MTTP (microsomal triglyceride transfer protein), is characterized by undetectable concentrations of apolipoprotein B, extremely low levels of low-density lipoprotein cholesterol in the plasma, and a total inability to export apolipoprotein B-containing lipoproteins from both the intestine and the liver. OBJECTIVE: To study lipid absorption after a fat load and liver function in 7 heterozygous relatives from 2 abetalipoproteinemic families, 1 previously unreported. RESULTS: Both patients are compound heterozygotes for p.(Arg540His) and either c.708\₇09del p.(His236Glnfs*11) or c.1344+3\₁344+6del on the MTTP gene. The previously undescribed patient has been followed for 22 years with ultrastructure analyses of both the intestine and the liver. In these 2 families, 5 relatives were heterozygous for p.(Arg540His), 1 for p.(His236Glnfs*11) and 1 for c.1344+3\₁344+6del. In 4 heterozygous relatives, the lipid absorption was normal independent of the MTTP variant. In contrast, in 3 of them, the increase in triglyceride levels after fat load was abnormal. These subjects were additionally heterozygous carriers of Asp2213 APOB in-frame deletion, near the cytidine mRNA editing site, which is essential for intestinal apoB48 production. Liver function appeared to be normal in all the heterozygotes except for one who exhibited liver steatosis for unexplained reasons. CONCLUSION: Our study suggests that a single copy of the MTTP gene may be sufficient for human normal lipid absorption, except when associated with an additional APOB gene alteration. The hepatic steatosis reported in 1 patient emphasizes the need for liver function tests in all heterozygotes until the level of risk is established.
Databáze: OpenAIRE
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