{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:47:18Z","timestamp":1791287238645,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the\n              <jats:italic>IDOL<\/jats:italic>\n              gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+\/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.119.312589","type":"journal-article","created":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T09:00:45Z","timestamp":1570698045000},"page":"2468-2479","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["IDOL G51S Variant Is Associated With High Blood Cholesterol and Increases Low-Density Lipoprotein Receptor Degradation"],"prefix":"10.1161","volume":"39","author":[{"given":"Dilare","family":"Adi","sequence":"first","affiliation":[{"name":"From the Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China (D.A., Z.-Y.F., G.B., Y.-T.M.)"},{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China 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