LIMA1 is a key protein regulating intestinal cholesterol absorption and is specifically expressed in the small intestine. A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. LDL-C concentration is influenced by environmental and genetic factors. The genetic factors affecting LDL-C are not fully characterized.
On June 8, 2018,Science published an article called A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption. The article showed that inhibiting LIMA1 can reduce cholesterol absorption and help treat hypercholesterolemia.
In this study, a family of low-LDL-C Kazakh ancestry was analyzed, and a special gene mutationwas successfully isolated— LIMA1 mutation. Individuals with low LDL-C levels in the blood carry the LIMA1 gene mutation.Those without the mutation had normal LDL-C levels.This mutation causes the production of the LIMA1. LIMA1-deficient mice display lower dietary cholesterol absorption.LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake.
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