<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Nomura, Akihiro</style></author><author><style face="normal" font="default" size="100%">Emdin, Connor A</style></author><author><style face="normal" font="default" size="100%">Won, Hong Hee</style></author><author><style face="normal" font="default" size="100%">Peloso, Gina M</style></author><author><style face="normal" font="default" size="100%">Natarajan, Pradeep</style></author><author><style face="normal" font="default" size="100%">Ardissino, Diego</style></author><author><style face="normal" font="default" size="100%">Danesh, John</style></author><author><style face="normal" font="default" size="100%">Schunkert, Heribert</style></author><author><style face="normal" font="default" size="100%">Correa, Adolfo</style></author><author><style face="normal" font="default" size="100%">Bown, Matthew J</style></author><author><style face="normal" font="default" size="100%">Samani, Nilesh J</style></author><author><style face="normal" font="default" size="100%">Erdmann, Jeanette</style></author><author><style face="normal" font="default" size="100%">McPherson, Ruth</style></author><author><style face="normal" font="default" size="100%">Watkins, Hugh</style></author><author><style face="normal" font="default" size="100%">Saleheen, Danish</style></author><author><style face="normal" font="default" size="100%">Elosua, Roberto</style></author><author><style face="normal" font="default" size="100%">Kawashiri, Masa-Aki</style></author><author><style face="normal" font="default" size="100%">Tada, Hayato</style></author><author><style face="normal" font="default" size="100%">Gupta, Namrata</style></author><author><style face="normal" font="default" size="100%">Shah, Svati H</style></author><author><style face="normal" font="default" size="100%">Rader, Daniel J</style></author><author><style face="normal" font="default" size="100%">Gabriel, Stacey</style></author><author><style face="normal" font="default" size="100%">Khera, Amit V</style></author><author><style face="normal" font="default" size="100%">Kathiresan, Sekar</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Heterozygous  Gene Deficiency and Risk of Coronary Artery Disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Circ Genom Precis Med</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Circ Genom Precis Med</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 10</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">13</style></volume><pages><style face="normal" font="default" size="100%">417-423</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Familial sitosterolemia is a rare Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Affected individuals typically have complete genetic deficiency-homozygous loss-of-function (LoF) variants-in the  or  genes and have substantially elevated plasma sitosterol and LDL (low-density lipoprotein) cholesterol (LDL-C) levels. The impact of partial genetic deficiency of  or -as occurs in heterozygous carriers of LoF variants-on LDL-C and risk of coronary artery disease (CAD) has remained uncertain.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;We first recruited 9 sitosterolemia families, identified causative LoF variants in  or , and evaluated the associations of these  or  LoF variants with plasma phytosterols and lipid levels. We next assessed for LoF variants in  or  in CAD cases (n=29 321) versus controls (n=357 326). We tested the association of rare LoF variants in  or  with blood lipids and risk for CAD. Rare LoF variants were defined as protein-truncating variants with minor allele frequency &lt;0.1% in  or .&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;In sitosterolemia families, 7 pedigrees harbored causative LoF variants in  and 2 pedigrees in . Homozygous LoF variants in either  or  led to marked elevations in sitosterol and LDL-C. Of those sitosterolemia families, heterozygous carriers of  LoF variants exhibited increased sitosterol and LDL-C levels compared with noncarriers. Within large-scale CAD case-control cohorts, prevalence of rare LoF variants in  and in  was ≈0.1% each.  heterozygous LoF variant carriers had significantly elevated LDL-C levels (25 mg/dL [95% CI, 14-35]; =1.1×10) and were at 2-fold increased risk of CAD (odds ratio, 2.06 [95% CI, 1.27-3.35]; =0.004). By contrast,  heterozygous LoF carrier status was not associated with increased LDL-C or risk of CAD.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Although familial sitosterolemia is traditionally considered as a recessive disorder, we observed that heterozygous carriers of an LoF variant in  had significantly increased sitosterol and LDL-C levels and a 2-fold increase in risk of CAD.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32862661?dopt=Abstract</style></custom1></record></records></xml>