Prevalence and Impact of Apolipoprotein E7 on LDL Cholesterol Among Patients With Familial Hypercholesterolemia.
Prevalence and Impact of Apolipoprotein E7 on LDL Cholesterol Among Patients With Familial Hypercholesterolemia.
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DOI：
10.3389/fcvm.2021.625852
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发表时间：
2021
影响因子：
3.6
通讯作者：
Kawashiri MA
中科院分区：
文献类型：
--
作者：
Tada H;Yamagami K;Kojima N;Shibayama J;Nishikawa T;Okada H;Nomura A;Usui S;Sakata K;Takamura M;Kawashiri MA
背景：有人认为，一种罕见的突变载脂蛋白 E7，APOE7（p.Glu262Lys，p.Glu263Lys）已被确定与普通人群的高脂蛋白血症有关。此外，其患病率已显示为 0.005-0.06%。然而，之前没有关于其患病率及其对家族性高胆固醇血症（FH）患者血脂影响的数据。方法：我们招募了 1,138 名临床诊断为 FH 的患者[平均年龄 = 48，男性 = 512，中位低密度脂蛋白 (LDL) 胆固醇 = 231 mg/dl]。对三个 FH 基因（LDLR、APOB 和 PCSK9）和载脂蛋白 E (APOE) 基因的编码区进行了测序。我们调查了 APOE7 突变体对 FH 患者血脂水平的影响。结果：我们鉴定出 29 名患者 (2.5%) 携带 APOE7 突变（杂合子），明显高于一般人群。此外，当我们关注那些没有 FH 突变的患者 (n = 540) 时，我们发现 21 名患者 (3.9%) 患有 APOE7 突变。与没有这种罕见突变体的患者相比，具有突变型 APOE7 的患者表现出显着更高的中位 LDL 胆固醇和甘油三酯水平（分别为 249 与 218 mg/dl，p < 0.05；216 与 164 mg/dl，p < 0.05）。此外，具有 FH 基因致病性突变和 APOE7 突变体的 APOE7 寡基因型 FH 个体的 LDL 胆固醇水平显着高于单基因 FH 患者（265 与 245 mg/dl，p < 0.05）。结论：我们在临床诊断为 FH 的患者中发现了比预期更多的 APOE7 突变患者，特别是在没有引起 FH 突变的患者中。这意味着 APOE7 突变可能是 FH 的原因之一，尤其是那些没有 FH 突变的人。
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.
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影响因子：
4.4
作者：
Harada-Shiba M;Arai H;Ishigaki Y;Ishibashi S;Okamura T;Ogura M;Dobashi K;Nohara A;Bujo H;Miyauchi K;Yamashita S;Yokote K;Working Group by Japan Atherosclerosis Society for Making Guidance of Familial Hypercholesterolemia
通讯作者：
Working Group by Japan Atherosclerosis Society for Making Guidance of Familial Hypercholesterolemia
影响因子：
5.3
作者：
KITAHARA, M;SHINOMIYA, M;YOSHIDA, S
通讯作者：
YOSHIDA, S
DOI：
10.1007/bf01874050
发表时间：
1994-09-01
期刊：
JAPANESE JOURNAL OF HUMAN GENETICS
影响因子：
--
作者：
YAMANOUCHI, Y;ARINAMI, T;HAMAGUCHI, H
通讯作者：
HAMAGUCHI, H
影响因子：
24
作者：
Sturm, Amy C.;Knowles, Joshua W.;Rader, Daniel J.
通讯作者：
Rader, Daniel J.
影响因子：
5.3
作者：
SOUTAR, AK;MYANT, NB;THOMPSON, GR
通讯作者：
THOMPSON, GR