A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption

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 LIMA1 (also known as EPLIN or SREBP3) 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, Lima1-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.

Source: ScienceNOW - June 7, 2018 Category: Science Authors: Zhang, Y.-Y., Fu, Z.-Y., Wei, J., Qi, W., Baituola, G., Luo, J., Meng, Y.-J., Guo, S.-Y., Yin, H., Jiang, S.-Y., Li, Y.-F., Miao, H.-H., Liu, Y., Wang, Y., Li, B.-L., Ma, Y.-T., Song, B.-L. Tags: Genetics, Medicine, Diseases r-articles Source Type: news