Science (American Association for the Advancement of Science), 2018-06, Vol.360 (6393), p.1087-1092
2018
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Details
- Autor(en) / Beteiligte
- Titel
- A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption
- Ist Teil von
- Science (American Association for the Advancement of Science), 2018-06, Vol.360 (6393), p.1087-1092
- Ort / Verlag
- United States: The American Association for the Advancement of Science
- Erscheinungsjahr
- 2018
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the (also known as or ) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane. LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake. Similar to the human phenotype, -deficient mice displayed reduced cholesterol absorption and were resistant to diet-induced hypercholesterolemia. Through our study of both mice and humans, we identify LIMA1 as a key protein regulating intestinal cholesterol absorption.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.aao6575Titel-ID: cdi_proquest_miscellaneous_2052805596
- Format
- –
- Schlagworte
- Absorption, Animals, Asian Continental Ancestry Group - genetics, Bile, Cardiovascular disease, Cardiovascular diseases, China, Cholesterol, Cholesterol, LDL - blood, Cholesterol, LDL - metabolism, Cytoskeletal Proteins - genetics, Cytoskeletal Proteins - metabolism, Frameshift Mutation, Genetic factors, Genetic Variation, Health risks, Hep G2 Cells, Humans, Hypercholesterolemia, Intestinal Absorption - genetics, Intestinal Mucosa - metabolism, Kazakhstan - ethnology, Lipid metabolism, Low density lipoprotein, Membrane Proteins - metabolism, Metabolism, Mice, Mice, Knockout, Minority & ethnic groups, Myocardial infarction, Myosin, Myosin Heavy Chains - metabolism, Myosin Type V - metabolism, Pedigree, Pharmacology, Phenotypes, Protein Binding, Protein Transport, Proteins, Risk factors, Rodents, Small intestine