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

Frontiers in Cardiovascular Medicine

article

Hayato Tada¹  Nobuko Kojima¹  Junichi Shibayama¹  Tetsuo Nishikawa¹  Hirofumi Okada¹  Akihiro Nomura¹  Soichiro Usui¹  Kenji Sakata¹  Masayuki Takamura¹  Masa-aki Kawashiri¹ 

[1] Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences

关键词: APOE;    familial hypercholesterolemia;    PCSK9;    LDLR;    LDL-C;   

DOI  :  10.3389/fcvm.2021.625852

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Background: 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). Methods: 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 ( LDLR, APOB , and PCSK9 ) and apolipoprotein E ( APOE ) gene were sequenced. We investigated the prevalence and impact of APOE7 mutant on serum lipid levels in patients with FH. Results: 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 ( n = 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, p < 0.05, 216 vs. 164 mg/dl, p < 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, p < 0.05). Conclusion: 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.

【 授权许可】

CC BY