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By studying a cohort of ApoB<jats:sup>R3500Q<\/jats:sup> heterozygotes and homozygotes, we aimed to characterize the biochemical and cardiac imaging features in children and young adults with a common genetic background and similar lifestyle.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We employed advanced lipid profile testing, carotid intima media thickness (CIMT), pulse wave velocity (PWV), and peripheral artery tonometry (PAT) to assess atherosclerosis in a cohort of Amish ApoB<jats:sup>R3500Q<\/jats:sup> heterozygotes (n\u2009=\u200913), homozygotes (n\u2009=\u20093), and their unaffected, age-matched siblings (n\u2009=\u20099). ApoB<jats:sup>R3500Q<\/jats:sup> homozygotes were not included in statistical comparisons.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>LDL cholesterol (LDL-C) was significantly elevated among ApoB<jats:sup>R3500Q<\/jats:sup> heterozygotes compared to sibling controls, though several ApoB<jats:sup>R3500Q<\/jats:sup> heterozygotes had LDL-C levels in the normal range. LDL particles (LDL-P), small, dense LDL particles, and ApoB were also significantly elevated among subjects with ApoB<jats:sup>R3500Q<\/jats:sup>. Despite these differences in serum lipids and particles, CIMT and PWV were not significantly different between ApoB<jats:sup>R3500Q<\/jats:sup> heterozygotes and controls in age-adjusted analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We provide a detailed description of the serum lipids, atherosclerotic plaque burden, vascular stiffness, and endothelial function among children and young adults with FH due to heterozygous ApoB<jats:sup>R3500Q<\/jats:sup>. Fasting LDL-C was lower than what is seen with other forms of FH, and even normal in several ApoB<jats:sup>R3500Q<\/jats:sup> heterozygotes, emphasizing the importance of cascade genetic testing among related individuals for diagnosis. We found increased number of LDL particles among ApoB<jats:sup>R3500Q<\/jats:sup> heterozygotes but an absence of detectable atherosclerosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12872-022-02539-3","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T11:03:04Z","timestamp":1647514984000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical characterization of familial hypercholesterolemia due to an amish founder mutation in Apolipoprotein B"],"prefix":"10.1186","volume":"22","author":[{"given":"Katie B.","family":"Williams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Horst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Millie","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Pascua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik G.","family":"Puffenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlla W.","family":"Brigatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Gonzaga-Jauregui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Shuldiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Gidding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Strauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devyani","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"issue":"36","key":"2539_CR1","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1093\/eurheartj\/ehv157","volume":"36","author":"A Wiegman","year":"2015","unstructured":"Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, et al. 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Written informed consent was obtained from study participants age 18\u00a0years and older to participate in the research study. Written informed consent was obtained from parents on behalf of their children age less than 18\u00a0years to participate in the research study. Study was conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SG serves as a consultant for Esperion Therapeutics, Inc. and as part of the advisory board for Silence Therapeutics. ARS and CGJ are employees of Regeneron Pharmaceuticals, Inc. and receive compensation in the form of salary and stock incentives for their employment. Remaining authors have no declarations of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"109"}}