aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.52727/2078-256X-2025-21-4-453-464ateroskleroz-1153Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSМикросомальный белок-переносчик триглицеридов: молекулярная генетика, функциональные механизмы и клиническое значениеMicrosomal triglyceride transfer protein: molecular genetics, functional mechanisms, and clinical significancehttps://orcid.org/0000-0002-5378-2128АсекритоваА. С.AsekritovaA. S.

Александра Степановна Асекритова, зав. Центром предиктивной медицины и биоинформатики

677027, Республика Саха (Якутия), г. Якутск, ул. Горького, 94;

доцент кафедры «Внутренние болезни и общей врачебной подготовки (семейная медицина)», Медицинского института

677000, Республика Саха (Якутия), г. Якутск, ул. Белинского, 58

Alexandra S. Asekritova, head of center for predictive medicine and bioinformatics, сandidate of medical sciences, associate professor of the Department of therapy, Institute of Medicine

94, Gorkogo ыt., Yakutsk, Republic of Sakha (Yakutia), 677027

58, Belinskogo st., Yakutsk, Republic of Sakha (Yakutia), 677000

my@asekritova-8.ruhttps://orcid.org/0009-0002-0773-3744ПавловаА. В.PavlovaA. V.

Анна Владимировна Павлова, кардиолог Центра предиктивной медицины и биоинформатики

677027, Республика Саха (Якутия), г. Якутск, ул. Горького, 94

Anna V. Pavlova, chief cardiologist of center for predictive medicine and bioinformatics

94, Gorkogo ыt., Yakutsk, Republic of Sakha (Yakutia), 677027

pavlovaav11@mail.ruhttps://orcid.org/0000-0002-0897-5473МихайловаС. В.MikhailovaS. V.

Светлана Владимировна Михайлова, научный сотрудник лаборатории молекулярной генетики человека

630090, г. Новосибирск, пр. Академика Лаврентьева, 10

Svetlana V. Mikhailova, researcher at the laboratory of human molecular genetics

10, Lavrentyeva ave., Novosibirsk, 630090

mikhail@bionet.nsc.ruhttps://orcid.org/0000-0002-0403-545XИванощукД. Е.IvanoshchukD. E.

Иванощук Динара Евгеньевна, младший научный сотрудник лаборатории молекулярной генетики человека

630090, г. Новосибирск, пр. Академика Лаврентьева, 10

Dinara E. Ivanoshchuk, junior researcher at the laboratory of human molecular genetics

10, Lavrentyeva ave., Novosibirsk, 630090

dinara@bionet.nsc.ruГосударственное автономное учреждение республики Саха (Якутия) Республиканская клиническая больница № 3; Федеральное государственное автономное образовательное учреждение высшего образования «Северо-Восточный федеральный университет им. М.К. Аммосова»Government Autonomous Institution of the Republic of Sakha (Yakutia) "Republican Clinical Hospital No.3; Federal State Autonomous Educational Institution of Higher Education «M.K. Ammosov Northeastern Federal University»Государственное автономное учреждение республики Саха (Якутия) Республиканская клиническая больница № 3Government Autonomous Institution of the Republic of Sakha (Yakutia) "Republican Clinical Hospital No.3Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences202524012026214453464Copyright © Асекритова А.С., Павлова А.В., Михайлова С.В., Иванощук Д.Е., 20252025Асекритова А.С., Павлова А.В., Михайлова С.В., Иванощук Д.Е.Asekritova A.S., Pavlova A.V., Mikhailova S.V., Ivanoshchuk D.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/1153

Цель настоящей работы – провести комплексный обзор структурно-функциональной организации гена MTTP и кодируемого им микросомального белка‑переносчика триглицеридов (МБПТ), охарактеризовать его патогенные варианты и описать молекулярные механизмы их действия. МБПТ является ключевым регулятором липидного обмена, необходимым для сборки и секреции apoB‑содержащих липопротеинов в гепатоцитах и энтероцитах. Биаллельные патогенные варианты гена MTTP вызывают абеталипопротеинемию – редкое жизнеугрожающее заболевание с прогрессирующими неврологическими и офтальмологическими осложнениями. Распространенные варианты гена ассоциированы с различными метаболическими нарушениями. Проведен обзор литературы с анализом структуры и механизмов альтернативного сплайсинга гена MTTP, доменной организации белка МБПТ, его взаимодействия с протеин‑дисульфид‑изомеразой, и некоторых патогенных вариантов этого гена на основе опубликованных функциональных исследований и клинических данных. Углубленное понимание молекулярных механизмов дисфункции МБПТ необходимо для корректной интерпретации результатов генетического тестирования, прогнозирования клинического фенотипа, проведения дифференциальной диагностики и разработки персонализированных терапевтических стратегий при абеталипопротеинемии и ассоциированных с ней нарушениях.

The aim of this work is to provide a comprehensive review of the structural and functional organization of the MTTP gene and the microsomal triglyceride transfer protein (MTP) it encodes, to characterize its pathogenic variants, and to describe the molecular mechanisms of their action. The MTP is a key regulator of lipid metabolism that is required for the assembly and secretion of apoB‑containing lipoproteins in hepatocytes and enterocytes. Biallelic pathogenic variants in MTTP cause abetalipoproteinemia, a rare life‑threatening disorder with progressive neurological and ophthalmological complications. Several common single nucleotide variants in this gene are associated with various metabolic disturbances. A literature review was conducted, including analysis of the gene structure and mechanisms of alternative splicing of MTTP, the domain organization of MTP, its interaction with protein disulfide isomerase, and selected pathogenic variants of this gene based on published functional studies and clinical data. An in‑depth understanding of the molecular mechanisms underlying MTP dysfunction is essential for accurate interpretation of genetic testing results, prediction of clinical phenotype, differential diagnosis, and the development of personalized therapeutic strategies for abetalipoproteinemia and related disorders.

ген MTTPмикросомальный белок-переносчик триглицеридовпротеиндисульфид-изомеразаабеталипопротеинемиягенетические вариантыMTTP genemicrosomal triglyceride transfer proteinprotein disulfide isomeraseabetalipoproteinemiagenetic variantsРабота выполнена в рамках темы Государственного задания FWNR-2022-0021.This research was conducted with the financial support of the State Budget Project FWNR2022-0021.ReferencesHussain M.M., Shi J., Dreizen P. Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly. J. Lipid Research, 2003; 44 (1): 22–32. doi: 10.1194/jlr.R200014-JLR200Hussain M.M., Shi J., Dreizen P. Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly. J. Lipid Research, 2003; 44 (1): 22–32. doi: 10.1194/jlr.R200014-JLR200Rustaeus S., Stillemark P., Lindberg K., Gordon D., Olofsson S.O. The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells. J. Biol. Chem., 1998; 273 (9): 5196–5203. doi: 10.1074/jbc.273.9.5196Rustaeus S., Stillemark P., Lindberg K., Gordon D., Olofsson S.O. The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells. J. Biol. Chem., 1998; 273 (9): 5196–5203. doi: 10.1074/jbc.273.9.5196Hussain M.M. A proposed model for the assembly of chylomicrons. Atherosclerosis, 2000; 148 (1): 1–15. doi: 10.1016/s0021-9150(99)00397-4Hussain M.M. A proposed model for the assembly of chylomicrons. Atherosclerosis, 2000; 148 (1): 1–15. doi: 10.1016/s0021-9150(99)00397-4Raabe M., Veniant M.M., Sullivan M.A., Zlot C.H., Björkegren J., Nielsen L.B., Wong J.S., Hamilton R.L., Young S.G. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J. Clin. Investigat., 1999; 103 (9): 1287–1298. doi: 10.1172/JCI6576Raabe M., Veniant M.M., Sullivan M.A., Zlot C.H., Björkegren J., Nielsen L.B., Wong J.S., Hamilton R.L., Young S.G. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J. Clin. Investigat., 1999; 103 (9): 1287–1298. doi: 10.1172/JCI6576Jamil H., Dickson J.K., Jr., Chu C.H., Lago M.W., Rinehart J.K., Biller S.A., Gregg R.E., Wetterau J.R. Microsomal triglyceride transfer protein. Specificity of lipid binding and transport. J. Biol. Chem., 1995; 270 (12): 6549–6554. doi: 10.1074/jbc.270.12.6549Jamil H., Dickson J.K., Jr., Chu C.H., Lago M.W., Rinehart J.K., Biller S.A., Gregg R.E., Wetterau J.R. Microsomal triglyceride transfer protein. Specificity of lipid binding and transport. J. Biol. Chem., 1995; 270 (12): 6549–6554. doi: 10.1074/jbc.270.12.6549Bassen F.A., Kornzweig A.L. Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood., 1950; 5 (4): 381–387. doi: 10.1182/blood.V5.4.381.381Bassen F.A., Kornzweig A.L. Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood., 1950; 5 (4): 381–387. doi: 10.1182/blood.V5.4.381.381Burnett J.R., Bell D.A., Hooper A.J., Hegele R.A. Clinical utility gene card for: Abetalipoproteinaemia – Update 2014. Eur. J. Hum. Genet., 2015; 23 (6): 890. doi: 10.1038/ejhg.2014.224Burnett J.R., Bell D.A., Hooper A.J., Hegele R.A. Clinical utility gene card for: Abetalipoproteinaemia – Update 2014. Eur. J. Hum. Genet., 2015; 23 (6): 890. doi: 10.1038/ejhg.2014.224Hentati F., El-Euch G., Bouhlal Y., Amouri R. Ataxia with vitamin E deficiency and abetalipoproteinemia. Handb. Clin. Neurol., 2012; 103: 295–305. doi: 10.1016/B978-0-444-51892-7.00018-8Hentati F., El-Euch G., Bouhlal Y., Amouri R. Ataxia with vitamin E deficiency and abetalipoproteinemia. Handb. Clin. Neurol., 2012; 103: 295–305. doi: 10.1016/B978-0-444-51892-7.00018-8Lee J., Hegele R.A. Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management. J. Inherit. Metab. Dis., 2014; 37 (3): 333–339. doi: 10.1007/s10545-013-9665-4Lee J., Hegele R.A. Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management. J. Inherit. Metab. Dis., 2014; 37 (3): 333–339. doi: 10.1007/s10545-013-9665-4Takahashi M., Okazaki H., Ohashi K., Ogura M., Ishibashi S., Okazaki S., Hirayama S., Hori M., Matsuki K., Yokoyama S., Harada-Shiba M. Current Diagnosis and Management of Abetalipoproteinemia. J. Atheroscler. Thromb., 2021; 28 (10): 1009–1019. doi: 10.5551/jat.RV17056Takahashi M., Okazaki H., Ohashi K., Ogura M., Ishibashi S., Okazaki S., Hirayama S., Hori M., Matsuki K., Yokoyama S., Harada-Shiba M. Current Diagnosis and Management of Abetalipoproteinemia. J. Atheroscler. Thromb., 2021; 28 (10): 1009–1019. doi: 10.5551/jat.RV17056Rodríguez Gutiérrez P.G., González García J.R., Castillo de León Y.A., Zárate Guerrero J.R., Magaña Torres M.T. A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases. J. Clin. Lab. Anal., 2021; 35 (3): e23672. doi: 10.1002/jcla.23672Rodríguez Gutiérrez P.G., González García J.R., Castillo de León Y.A., Zárate Guerrero J.R., Magaña Torres M.T. A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases. J. Clin. Lab. Anal., 2021; 35 (3): e23672. doi: 10.1002/jcla.23672Sharp D., Ricci B., Kienzle B., Lin M.C., Wetterau J.R. Human microsomal triglyceride transfer protein large subunit gene structure. Biochemistry, 1994; 33(31): 9057–9061. doi: 10.1021/bi00197a005Sharp D., Ricci B., Kienzle B., Lin M.C., Wetterau J.R. Human microsomal triglyceride transfer protein large subunit gene structure. Biochemistry, 1994; 33(31): 9057–9061. doi: 10.1021/bi00197a005Suzuki T., Swift L.L. Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues. Sci. Rep., 2016; 6: 27308. doi: 10.1038/srep27308Suzuki T., Swift L.L. Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues. Sci. Rep., 2016; 6: 27308. doi: 10.1038/srep27308Biterova E.I., Isupov M.N., Keegan R.M., Lebedev A.A., Sohail A.A., Liaqat I., Alanen H.I., Ruddock L.W. The crystal structure of human microsomal triglyceride transfer protein. Proc. Natl. Acad. Sci. USA., 2019; 116 (35): 17251–17260. doi: 10.1073/pnas.1903029116Biterova E.I., Isupov M.N., Keegan R.M., Lebedev A.A., Sohail A.A., Liaqat I., Alanen H.I., Ruddock L.W. The crystal structure of human microsomal triglyceride transfer protein. Proc. Natl. Acad. Sci. USA., 2019; 116 (35): 17251–17260. doi: 10.1073/pnas.1903029116Rehberg E.F., Samson-Bouma M.E., Kienzle B., Blinderman L., Jamil H., Wetterau J.R., Aggerbeck L.P., Gordon D.A. A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase. J. Biol. Chem., 1996; 271 (47): 29945–29952. doi: 10.1074/jbc.271.47.29945Rehberg E.F., Samson-Bouma M.E., Kienzle B., Blinderman L., Jamil H., Wetterau J.R., Aggerbeck L.P., Gordon D.A. A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase. J. Biol. Chem., 1996; 271 (47): 29945–29952. doi: 10.1074/jbc.271.47.29945Hussain M.M., Rava P., Walsh M., Rana M., Iqbal J. Multiple functions of microsomal triglyceride transfer protein. Nutr. Metab. (Lond.), 2012; 9: 14. doi: 10.1186/1743-7075-9-14Hussain M.M., Rava P., Walsh M., Rana M., Iqbal J. Multiple functions of microsomal triglyceride transfer protein. Nutr. Metab. (Lond.), 2012; 9: 14. doi: 10.1186/1743-7075-9-14Wetterau J.R., Combs K.A., Spinner S.N., Joiner B.J. Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex. J. Biol. Chem., 1990; 265,(17): 9800–9807Wetterau J.R., Combs K.A., Spinner S.N., Joiner B.J. Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex. J. Biol. Chem., 1990; 265,(17): 9800–9807Klappa P., Ruddock L.W., Darby N.J., Freedman R.B. The b’ domain provides the principal peptide-binding site of protein disulfide isomerase but all domains contribute to binding of misfolded proteins. EMBO J., 1998; 17 (4): 927–935. doi: 10.1093/emboj/17.4.927Klappa P., Ruddock L.W., Darby N.J., Freedman R.B. The b’ domain provides the principal peptide-binding site of protein disulfide isomerase but all domains contribute to binding of misfolded proteins. EMBO J., 1998; 17 (4): 927–935. doi: 10.1093/emboj/17.4.927Ellgaard L., Ruddock L.W. The human protein disulphide isomerase family: substrate interactions and functional properties. EMBO Rep., 2005; 6 (1): 28–32. doi: 10.1038/sj.embor.7400311Ellgaard L., Ruddock L.W. The human protein disulphide isomerase family: substrate interactions and functional properties. EMBO Rep., 2005; 6 (1): 28–32. doi: 10.1038/sj.embor.7400311Chen F., Yang A., Lu Y., Zhang Y., Zhang J., Bu J., Guo R., Han Y., Wu D., Wu Y. Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes. Nat. Commun., 2025; 16 (1): 1344. doi: 10.1038/s41467-025-56620-4Chen F., Yang A., Lu Y., Zhang Y., Zhang J., Bu J., Guo R., Han Y., Wu D., Wu Y. Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes. Nat. Commun., 2025; 16 (1): 1344. doi: 10.1038/s41467-025-56620-4Munro S., Pelham H.R. A C-terminal signal prevents secretion of luminal ER proteins. Cell, 1987; 48 (5): 899–907. doi: 10.1016/0092-8674(87)90086-9Munro S., Pelham H.R. A C-terminal signal prevents secretion of luminal ER proteins. Cell, 1987; 48 (5): 899–907. doi: 10.1016/0092-8674(87)90086-9Mann C.J., Anderson T.A., Read J., Chester S.A., Harrison G.B., Köchl S., Ritchie P.J., Bradbury P., Hussain F.S., Amey J., Vanloo B., Rosseneu M., Infante R., Hancock J.M., Levitt D.G., Banaszak L.J., Scott J., Shoulders C.C. The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins. J. Mol. Biol., 1999; 285 (1): 391–408. doi: 10.1006/jmbi.1998.2298Mann C.J., Anderson T.A., Read J., Chester S.A., Harrison G.B., Köchl S., Ritchie P.J., Bradbury P., Hussain F.S., Amey J., Vanloo B., Rosseneu M., Infante R., Hancock J.M., Levitt D.G., Banaszak L.J., Scott J., Shoulders C.C. The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins. J. Mol. Biol., 1999; 285 (1): 391–408. doi: 10.1006/jmbi.1998.2298Bradbury P., Mann C.J., Köchl S., Anderson T.A., Chester S.A., Hancock J.M., Ritchie P.J., Amey J., Harrison G.B., Levitt D.G., Banaszak L.J., Scott J., Shoulders C.C. A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase. J. Biol. Chem., 1999; 274 (5): 3159–3164. doi: 10.1074/jbc.274.5.3159Bradbury P., Mann C.J., Köchl S., Anderson T.A., Chester S.A., Hancock J.M., Ritchie P.J., Amey J., Harrison G.B., Levitt D.G., Banaszak L.J., Scott J., Shoulders C.C. A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase. J. Biol. Chem., 1999; 274 (5): 3159–3164. doi: 10.1074/jbc.274.5.3159Rustaeus S., Stillemark P., Lindberg K., Gordon D., Olofsson S.O. The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells. J. Biol. Chem., 1998; 273 (9): 5196–5203. doi: 10.1074/jbc.273.9.5196Rustaeus S., Stillemark P., Lindberg K., Gordon D., Olofsson S.O. The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells. J. Biol. Chem., 1998; 273 (9): 5196–5203. doi: 10.1074/jbc.273.9.5196Sirwi A., Hussain M.M. Lipid transfer proteins in the assembly of apoB-containing lipoproteins. J. Lipid. Res., 2018; 59 (7): 1094–1102. doi: 10.1194/jlr.R083451Sirwi A., Hussain M.M. Lipid transfer proteins in the assembly of apoB-containing lipoproteins. J. Lipid. Res., 2018; 59 (7): 1094–1102. doi: 10.1194/jlr.R083451Thierer J.H., Foresti O., Yadav P.K., Wilson M.H., Moll T.O.C., Shen M.C., Busch-Nentwich E.M., Morash M., Mohlke K.L., Rawls J.F., Malhotra V., Hussain M.M., Farber S.A. Pla2g12b drives expansion of triglyceride-rich lipoproteins. Nat. Commun., 2024; 15 (1): 2095. doi: 10.1038/s41467-024-46102-4Thierer J.H., Foresti O., Yadav P.K., Wilson M.H., Moll T.O.C., Shen M.C., Busch-Nentwich E.M., Morash M., Mohlke K.L., Rawls J.F., Malhotra V., Hussain M.M., Farber S.A. Pla2g12b drives expansion of triglyceride-rich lipoproteins. Nat. Commun., 2024; 15 (1): 2095. doi: 10.1038/s41467-024-46102-4Fisher E., Lake E., McLeod R.S. Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion. J. Biomed. Res., 2014; 28 (3): 178–193. doi: 10.7555/JBR.28.20140019Fisher E., Lake E., McLeod R.S. Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion. J. Biomed. Res., 2014; 28 (3): 178–193. doi: 10.7555/JBR.28.20140019Iqbal J., Walsh M.T., Hammad S.M., Cuchel M., Tarugi P., Hegele R.A., Davidson N.O., Rader D.J., Klein R.L., Hussain M.M. Microsomal Triglyceride Transfer Protein Transfers and Determines Plasma Concentrations of Ceramide and Sphingomyelin but Not Glycosylceramide. J. Biol. Chem., 2015; 290 (43): 25863–25875. doi: 10.1074/jbc.M115.659110Iqbal J., Walsh M.T., Hammad S.M., Cuchel M., Tarugi P., Hegele R.A., Davidson N.O., Rader D.J., Klein R.L., Hussain M.M. Microsomal Triglyceride Transfer Protein Transfers and Determines Plasma Concentrations of Ceramide and Sphingomyelin but Not Glycosylceramide. J. Biol. Chem., 2015; 290 (43): 25863–25875. doi: 10.1074/jbc.M115.659110Rader D.J., Brewer H.B., Jr. Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. JAMA, 1993; 270 (7): 865–869. doi: 10.1001/jama.270.7.865Rader D.J., Brewer H.B., Jr. Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. JAMA, 1993; 270 (7): 865–869. doi: 10.1001/jama.270.7.865Valmiki S., Bredefeld C., Hussain M.M. A novel mutation, Ile344Asn, in microsomal triglyceride transfer protein abolishes binding to protein disulfide isomerase. J. Lipid. Res., 2025; 66 (1): 100725. doi: 10.1016/j.jlr.2024.100725Valmiki S., Bredefeld C., Hussain M.M. A novel mutation, Ile344Asn, in microsomal triglyceride transfer protein abolishes binding to protein disulfide isomerase. J. Lipid. Res., 2025; 66 (1): 100725. doi: 10.1016/j.jlr.2024.100725Benayoun L., Granot E., Rizel L., Allon-Shalev S., Behar D.M., Ben-Yosef T. Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient. Mol. Genet. Metab., 2007; 90 (4): 453–457. doi: 10.1016/j.ymgme.2006.12.010Benayoun L., Granot E., Rizel L., Allon-Shalev S., Behar D.M., Ben-Yosef T. Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient. Mol. Genet. Metab., 2007; 90 (4): 453–457. doi: 10.1016/j.ymgme.2006.12.010Ricci B., Sharp D., O’Rourke E., Kienzle B., Blinderman L., Gordon D., Smith-Monroy C., Robinson G., Gregg R.E., Rader D.J., Wetterau J.R. A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia. J. Biol. Chem., 1995; 270 (24): 14281–14285. doi: 10.1074/jbc.270.24.14281Ricci B., Sharp D., O’Rourke E., Kienzle B., Blinderman L., Gordon D., Smith-Monroy C., Robinson G., Gregg R.E., Rader D.J., Wetterau J.R. A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia. J. Biol. Chem., 1995; 270 (24): 14281–14285. doi: 10.1074/jbc.270.24.14281Walsh M.T., Iqbal J., Josekutty J., Soh J., Di Leo E., Özaydin E., Gündüz M., Tarugi P., Hussain M.M. Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal β-Barrel in Microsomal Triglyceride Transfer Protein Function. Circ. Cardiovasc. Genet., 2015; 8 (5): 677–687. doi: 10.1161/CIRCGENETICS.115.001106Walsh M.T., Iqbal J., Josekutty J., Soh J., Di Leo E., Özaydin E., Gündüz M., Tarugi P., Hussain M.M. Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal β-Barrel in Microsomal Triglyceride Transfer Protein Function. Circ. Cardiovasc. Genet., 2015; 8 (5): 677–687. doi: 10.1161/CIRCGENETICS.115.001106Khatun I., Walsh M.T., Hussain M.M. Loss of both phospholipid and triglyceride transfer activities of microsomal triglyceride transfer protein in abetalipoproteinemia. J. Lipid. Res., 2013; 54 (6): 1541–1549. doi: 10.1194/jlr.M031658Khatun I., Walsh M.T., Hussain M.M. Loss of both phospholipid and triglyceride transfer activities of microsomal triglyceride transfer protein in abetalipoproteinemia. J. Lipid. Res., 2013; 54 (6): 1541–1549. doi: 10.1194/jlr.M031658Miller S.A., Burnett J.R., Leonis M.A., McKnight C.J., van Bockxmeer F.M., Hooper A.J. Novel missense MTTP gene mutations causing abetalipoproteinemia. Biochim. Biophys. Acta., 2014; 1842 (10): 1548–1554. doi: 10.1016/j.bbalip.2014.08.001Miller S.A., Burnett J.R., Leonis M.A., McKnight C.J., van Bockxmeer F.M., Hooper A.J. Novel missense MTTP gene mutations causing abetalipoproteinemia. Biochim. Biophys. Acta., 2014; 1842 (10): 1548–1554. doi: 10.1016/j.bbalip.2014.08.001Di Filippo M., Varret M., Boehm V., Rabès J.P., Ferkdadji L., Abramowitz L., Dumont S., Lenaerts C., Boileau C., Joly F., Schmitz J., Samson-Bouma M.E., Bonnefont-Rousselot D. Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families. J. Clin. Lipidol., 2019; 13 (1): 201–212. doi: 10.1016/j.jacl.2018.10.003Di Filippo M., Varret M., Boehm V., Rabès J.P., Ferkdadji L., Abramowitz L., Dumont S., Lenaerts C., Boileau C., Joly F., Schmitz J., Samson-Bouma M.E., Bonnefont-Rousselot D. Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families. J. Clin. Lipidol., 2019; 13 (1): 201–212. doi: 10.1016/j.jacl.2018.10.003Paquette M., Dufour R., Hegele R.A., Baass A. A tale of 2 cousins: An atypical and a typical case of abetalipoproteinemia. J. Clin. Lipidol., 2016; 10 (4): 1030–1034. doi: 10.1016/j.jacl.2016.01.003Paquette M., Dufour R., Hegele R.A., Baass A. A tale of 2 cousins: An atypical and a typical case of abetalipoproteinemia. J. Clin. Lipidol., 2016; 10 (4): 1030–1034. doi: 10.1016/j.jacl.2016.01.003Di Filippo M., Créhalet H., Samson-Bouma M.E., Bonnet V., Aggerbeck L.P., Rabès J.P., Gottrand F., Luc G., Bozon D., Sassolas A. Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia. J. Lipid. Res., 2012; 53 (3): 548–555. doi: 10.1194/jlr.M020024Di Filippo M., Créhalet H., Samson-Bouma M.E., Bonnet V., Aggerbeck L.P., Rabès J.P., Gottrand F., Luc G., Bozon D., Sassolas A. Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia. J. Lipid. Res., 2012; 53 (3): 548–555. doi: 10.1194/jlr.M020024Wang J., Hegele R.A. Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia. Hum. Mutat., 2000; 15 (3): 294–295. doi: 10.1002/(SICI)1098-1004(200003)15:3<294::AID-HUMU14>3.0.CO;2-EWang J., Hegele R.A. Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia. Hum. Mutat., 2000; 15 (3): 294–295. doi: 10.1002/(SICI)1098-1004(200003)15:3<294::AID-HUMU14>3.0.CO;2-EOhashi K., Ishibashi S., Osuga J., Tozawa R., Harada K., Yahagi N., Shionoiri F., Iizuka Y., Tamura Y., Nagai R., Illingworth D.R., Gotoda T., Yamada N. Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia. J. Lipid. Res., 2000; 41 (8): 1199–1204Ohashi K., Ishibashi S., Osuga J., Tozawa R., Harada K., Yahagi N., Shionoiri F., Iizuka Y., Tamura Y., Nagai R., Illingworth D.R., Gotoda T., Yamada N. Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia. J. Lipid. Res., 2000; 41 (8): 1199–1204Gurram S., Holla V.V., Sriram N., Phulpagar P., Jha S., Sharma P., Mallithavana S., Kamble N., Netravathi M., Yadav R., Muthusamy B., Pal P.K. A Rare Case of Ophthalmoplegia with Ataxia in Genetically Proven Abetalipoproteinemia. Mov. Disord. Clin. Pract., 2022; 10 (3): 514–517. doi: 10.1002/mdc3.13626Gurram S., Holla V.V., Sriram N., Phulpagar P., Jha S., Sharma P., Mallithavana S., Kamble N., Netravathi M., Yadav R., Muthusamy B., Pal P.K. A Rare Case of Ophthalmoplegia with Ataxia in Genetically Proven Abetalipoproteinemia. Mov. Disord. Clin. Pract., 2022; 10 (3): 514–517. doi: 10.1002/mdc3.13626Grove J.I., Lo P.C.K., Shrine N., Barwell J., Wain L.V., Tobin M.D., Salter A.M., Borkar A.N., Cuevas-Ocaña S., Bennett N., John C., Ntalla I., Jones G.E., Neal C.P., Thomas M.G., Kuht H., Gupta P., Vemala V.M., Grant A., Adewoye A.B., Shenoy K.T., Balakumaran L.K., Hollox E.J., Hannan N.R.F., Aithal G.P. Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease. JHEP Rep., 2023; 5 (8): 100764. doi: 10.1016/j.jhepr.2023.100764Grove J.I., Lo P.C.K., Shrine N., Barwell J., Wain L.V., Tobin M.D., Salter A.M., Borkar A.N., Cuevas-Ocaña S., Bennett N., John C., Ntalla I., Jones G.E., Neal C.P., Thomas M.G., Kuht H., Gupta P., Vemala V.M., Grant A., Adewoye A.B., Shenoy K.T., Balakumaran L.K., Hollox E.J., Hannan N.R.F., Aithal G.P. Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease. JHEP Rep., 2023; 5 (8): 100764. doi: 10.1016/j.jhepr.2023.100764Sasaki K., Tada H., Komatsu T., Terada H., Endo Y., Ikewaki K., Uehara Y. A New Case of Abetalipoproteinemia Caused by Novel Compound Heterozygote Mutations in the MTTP Gene without Fat or Vitamin Malabsorption. J. Atheroscler. Thromb., 2024; 31 (11): 1634–1640. doi: 10.5551/jat.64730Sasaki K., Tada H., Komatsu T., Terada H., Endo Y., Ikewaki K., Uehara Y. A New Case of Abetalipoproteinemia Caused by Novel Compound Heterozygote Mutations in the MTTP Gene without Fat or Vitamin Malabsorption. J. Atheroscler. Thromb., 2024; 31 (11): 1634–1640. doi: 10.5551/jat.64730Gouda W., Ashour E., Shaker Y., Ezzat W. MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients. Genes Dis., 2017; 4 (4): 222–228. doi: 10.1016/j.gendis.2017.09.002Gouda W., Ashour E., Shaker Y., Ezzat W. MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients. Genes Dis., 2017; 4 (4): 222–228. doi: 10.1016/j.gendis.2017.09.002Peng X.E., Wu Y.L., Lu Q.Q., Hu Z.J., Lin X. MTTP polymorphisms and susceptibility to non-alcoholic fatty liver disease in a Han Chinese population. Liver Int., 2014; 34 (1): 118–128. doi: 10.1111/liv.12220Peng X.E., Wu Y.L., Lu Q.Q., Hu Z.J., Lin X. MTTP polymorphisms and susceptibility to non-alcoholic fatty liver disease in a Han Chinese population. Liver Int., 2014; 34 (1): 118–128. doi: 10.1111/liv.12220Ledmyr H., McMahon A.D., Ehrenborg E., Nielsen L.B., Neville M., Lithell H., MacFarlane P.W., Packard C.J., Karpe F.; WOSCOPS executive. The microsomal triglyceride transfer protein gene-493T variant lowers cholesterol but increases the risk of coronary heart disease. Circulation. 2004; 109 (19): 2279–2284. doi: 10.1161/01.CIR.0000130070.96758.7bLedmyr H., McMahon A.D., Ehrenborg E., Nielsen L.B., Neville M., Lithell H., MacFarlane P.W., Packard C.J., Karpe F.; WOSCOPS executive. The microsomal triglyceride transfer protein gene-493T variant lowers cholesterol but increases the risk of coronary heart disease. Circulation. 2004; 109 (19): 2279–2284. doi: 10.1161/01.CIR.0000130070.96758.7bdi Giuseppe R., Pechlivanis S., Fisher E., Arregui M., Weikert B., Knüppel S., Buijsse B., Fritsche A., Willich S.N., Joost H.G., Boeing H., Moebus S., Weikert C. Microsomal triglyceride transfer protein -164 T > C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study. BMC Med. Genet., 2013; 14: 19. doi: 10.1186/1471-2350-14-19di Giuseppe R., Pechlivanis S., Fisher E., Arregui M., Weikert B., Knüppel S., Buijsse B., Fritsche A., Willich S.N., Joost H.G., Boeing H., Moebus S., Weikert C. Microsomal triglyceride transfer protein -164 T > C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study. BMC Med. Genet., 2013; 14: 19. doi: 10.1186/1471-2350-14-19Rubin D., Helwig U., Pfeuffer M., Schreiber S., Boeing H., Fisher E., Pfeiffer A., Freitag-Wolf S., Foelsch U.R., Doering F., Schrezenmeir J. A common functional exon polymorphism in the microsomal triglyceride transfer protein gene is associated with type 2 diabetes, impaired glucose metabolism and insulin levels. J. Hum. Genet., 2006; 51 (6): 567–574. doi: 10.1007/s10038-006-0400-yRubin D., Helwig U., Pfeuffer M., Schreiber S., Boeing H., Fisher E., Pfeiffer A., Freitag-Wolf S., Foelsch U.R., Doering F., Schrezenmeir J. A common functional exon polymorphism in the microsomal triglyceride transfer protein gene is associated with type 2 diabetes, impaired glucose metabolism and insulin levels. J. Hum. Genet., 2006; 51 (6): 567–574. doi: 10.1007/s10038-006-0400-yWang X., Cao Y., Guo J., Li D., Zhang H., Song Q., Lu J. Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis. Lipids Health Dis., 2023; 22 (1): 154. doi: 10.1186/s12944-023-01916-xWang X., Cao Y., Guo J., Li D., Zhang H., Song Q., Lu J. Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis. Lipids Health Dis., 2023; 22 (1): 154. doi: 10.1186/s12944-023-01916-x

The authors declare that there are no conflicts of interest present.