AUTHOR=Tada Hayato , Yamagami Kan , Kojima Nobuko , Shibayama Junichi , Nishikawa Tetsuo , Okada Hirofumi , Nomura Akihiro , Usui Soichiro , Sakata Kenji , Takamura Masayuki , Kawashiri Masa-aki 

TITLE=Prevalence and Impact of Apolipoprotein E7 on LDL Cholesterol Among Patients With Familial Hypercholesterolemia

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.625852

DOI=10.3389/fcvm.2021.625852

ISSN=2297-055X

ABSTRACT=<p><bold>Background:</bold> It has been suggested that a rare mutant apolipoprotein E7, APOE7 (p.Glu262Lys, p.Glu263Lys), has been identified to be associated with hyperlipoproteinemia in the general population. Moreover, its prevalence has been shown to be 0.005–0.06%. However, there are no prior data regarding its prevalence and impact on serum lipids in patients with familial hypercholesterolemia (FH).</p><p><bold>Methods:</bold> We recruited 1,138 patients with clinically diagnosed FH [mean age = 48, men = 512, median low-density lipoprotein (LDL) cholesterol = 231 mg/dl]. The coding regions of three FH genes (<italic>LDLR, APOB</italic>, and <italic>PCSK9</italic>) and apolipoprotein E (<italic>APOE</italic>) gene were sequenced. We investigated the prevalence and impact of APOE7 mutant on serum lipid levels in patients with FH.</p><p><bold>Results:</bold> We identified 29 patients (2.5 %) with a mutant APOE7 (heterozygote), which is apparently much higher than that of the general population. Moreover, when we focus on those without FH mutation (<italic>n</italic> = 540), we identified 21 patients (3.9 %) with a mutant APOE7. Patients with a mutant APOE7 exhibited significantly higher median LDL cholesterol and triglyceride levels compared with those without this rare mutant (249 vs. 218 mg/dl, <italic>p</italic> &lt; 0.05, 216 vs. 164 mg/dl, <italic>p</italic> &lt; 0.05, respectively). Moreover, LDL cholesterol levels in the APOE7-oligogenic FH individuals, with a pathogenic mutation in FH genes and APOE7 mutant, were significantly higher than that in monogenic FH patients (265 vs. 245 mg/dl, <italic>p</italic> &lt; 0.05).</p><p><bold>Conclusion:</bold> We identified more patients with a mutant APOE7 than expected among those diagnosed with FH clinically, especially among those without FH-causing mutation. This implies a mutant APOE7 may be one of the causes FH, especially among those without FH mutations.</p>