{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:25:48Z","timestamp":1772166348971,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder of lipoprotein metabolism caused by pathogenic variants in both alleles of key low-density lipoprotein receptor (LDLR)-mediated pathway genes, resulting in very high LDL cholesterol (LDL-C) levels from birth. The microsomal triglyceride transfer protein (MTP) inhibitor lomitapide, is an effective treatment for lowering LDL-C in HoFH that acts independently of LDLR. This study investigated the response to lomitapide treatment and the potential impact of\n                      <jats:italic>MTTP<\/jats:italic>\n                      gene variants in a cohort of patients with HoFH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data were extracted from medical records of patients diagnosed with HoFH and receiving treatment with lomitapide in addition to background statin\u2009+\u2009ezetimibe\u2009+\u2009PCSK9 inhibitor therapy. Data on LDL-C levels before and after lomitapide treatment were collected from patient medical histories. Genetic sequencing of all exonic and intronic flanking regions of the\n                      <jats:italic>MTTP<\/jats:italic>\n                      gene was carried out for all patients with genomic DNA isolated from whole blood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 13 patients with a diagnosis of HoFH were identified (mean\u2009\u00b1\u2009standard deviation age, 47.3\u2009\u00b1\u200917.3 years). The median (range) dose of lomitapide was 20\u00a0mg\/day (10 to 60\u00a0mg\/day). Median (range) baseline LDL-C (before lomitapide) was 240\u00a0mg\/dL (162 to 478\u00a0mg\/dL). Following lomitapide treatment the median (range) LDL-C level was 119\u00a0mg\/dL (56 to 305\u00a0mg\/dL), and all patients reported a reduction in LDL-C with lomitapide. A total of 151\n                      <jats:italic>MTTP<\/jats:italic>\n                      gene variants were identified encompassing 50 distinct variants. There was a trend for more variants per patient with LDL-C reduction\u2009&gt;\u200950% vs. patients with LDL-C reduction\u2009\u2264\u200950% (difference, 8.5; 95% confidence interval [CI] \u2212\u20091.2, 18.1;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.08). Several\n                      <jats:italic>MTTP<\/jats:italic>\n                      gene variants (rs17533489, rs79194015, rs745075, rs41275715, rs1491246, and rs17533517) previously identified as potentially associated with a greater response to lomitapide treatment were significantly more common in patients with a reduction in LDL-C\u2009&gt;\u200950% than those with a reduction in LDL-C\u2009\u2264\u200950% (difference, 3.9; 95% CI 3.3, 4.5;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study builds upon previous findings by our group suggesting that variants in the\n                      <jats:italic>MTTP<\/jats:italic>\n                      gene may influence response to lomitapide. This study further presented a number of variants that may be uniquely associated with higher or lower response to lomitapide treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-04033-3","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:05:02Z","timestamp":1760450702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lomitapide response in a cohort of patients with homozygous familial hypercholesterolemia and the potential influence of MTTP gene variants"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-4555","authenticated-orcid":false,"given":"Genovefa","family":"Kolovou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vana","family":"Kolovou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Anagnostopoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Anastasiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petros","family":"Kalogeropoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelos","family":"Liberopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"issue":"32","key":"4033_CR1","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1093\/eurheartj\/ehu274","volume":"35","author":"M Cuchel","year":"2014","unstructured":"Cuchel M, Bruckert E, Ginsberg HN, et al. 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