未经证实:基因检测仍然很少用于诊断血脂异常,尽管决定血脂水平的基因变异并不少见。
UNASSIGNED:从与家族性高胆固醇血症(LDLR,APOB,PCSK9,HMGCR,APOE)在具有极高血浆浓度的低密度脂蛋白(LDL)胆固醇的受试者的心血管队列中,我们在APOB基因中发现并鉴定了一个新的点突变,这与极低水平的载脂蛋白B(ApoB)和LDL胆固醇有关。
UNASSIGNED:APOBc.6943G>T在APOB基因中的外显子26水平诱导过早终止密码子,并产生具有野生型ApoB-100(ApoB-51)质量的51%的蛋白质,在残基2315的水平上截断。过早的终止密码子出现在合成ApoB-48所需的终止密码子之后,从而允许在肠道水平产生乳糜微粒,从而避免潜在的营养损害。APOBc.6943G>T的杂合载体,尽管除血脂异常外,包括所有传统危险因素的风险非常高,冠状动脉造影正常,在20年随访期间未报告任何重大不良心血管事件,从而从基因变异中获得保护动脉粥样硬化的优势,显然没有任何代谢报复。
UNASSIGNED:我们的数据支持在特征明确的临床环境中使用靶向NGS,他们也表明了这一点。部分阻断ApoB的产生可能具有良好的耐受性并改善心血管结局.
UNASSIGNED: Genetic testing is still rarely used for the diagnosis of dyslipidemia, even though gene variants determining plasma lipids levels are not uncommon.
UNASSIGNED: Starting from a a pilot-analysis of targeted Next Generation Sequencing (NGS) of 5 genes related to familial hypercholesterolemia (LDLR, APOB, PCSK9, HMGCR, APOE) within a cardiovascular cohort in subjects with extreme plasma concentrations of low-density lipoprotein (LDL) cholesterol, we discovered and characterized a novel point mutation in the APOB gene, which was associated with very low levels of apolipoprotein B (ApoB) and LDL cholesterol.
UNASSIGNED: APOB c.6943 G > T induces a premature stop codon at the level of exon 26 in the APOB gene and generates a protein which has the 51% of the mass of the wild type ApoB-100 (ApoB-51), with a truncation at the level of residue 2315. The premature stop codon occurs after the one needed for the synthesis of ApoB-48, allowing chylomicron production at intestinal level and thus avoiding potential nutritional impairments. The heterozygous carrier of APOB c.6943G > T, despite a very high-risk profile encompassing all the traditional risk factors except for dyslipidemia, had normal coronary arteries by angiography and did not report any major adverse cardiovascular event during a 20-years follow-up, thereby obtaining advantage from the gene variant as regards protection against atherosclerosis, apparently without any metabolic retaliation.
UNASSIGNED: Our data support the use of targeted NGS in well-characterized clinical settings, as well as they indicate that.a partial block of ApoB production may be well tolerated and improve cardiovascular outcomes.