Systematic Analysis of Pathophysiology of Familial Hypercholesterolemia Due to Different Causal Gene Mutations

不同致病基因突变引起的家族性高胆固醇血症病理生理学的系统分析

• 批准号: 21591160
• 负责人: KAWASHIRI Masaaki
• 金额: $ 2.91万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591160/
• 关键词: 脂質代謝異常; 家族性高コレステロール血症; 安定同位体; 常染色体劣性高コレステロール血症; PCSK9

The fractional catabolic rate(FCR) of low-density lipoprotein(LDL) apolipoprotein B(apoB) in a patient with autosomal recessive hypercholesterolemia(ARH) was 75% smaller, whereas direct removal of very-LDL apoB was dramatically greater compared with those of normal control subjects. Statin therapy normalized FCR of LDL apoB and increased direct removal of very-LDL in ARH patient. On the other hand, the FCR of patients with homozygous proprotein convertase subtilisin/kexin 9(PCSK9) gene mutation was 52% smaller than that of normal control subjects and normalized by statin therapy. Whereas, both production rate and direct removal of very-LDL was increased compared with those of normal control subjects, which were not changed by statin therapy.

常染色体隐性高胆固醇血症（ARH）的患者中低密度脂蛋白（LDL）载脂蛋白B（APOB）的分数分解率（FCR）小于75％，而直接去除非常受试者的APOB的人数明显更大。他汀类药物治疗将LDL APOB的FCR归一化，并增加了ARH患者中极限局的直接去除。另一方面，纯合普罗蛋白转化酶枯草蛋白/KEXIN 9（PCSK9）基因突变的FCR比正常对照组小52％，并通过他汀类药物治疗进行了归一化。而与正常对照组受试者相比，生产率和直接去除非常LDL的速度均增加，而汀类药物治疗并未改变。

项目成果

Cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells to serum is preserved in CETP-deficient patients

• DOI: 10.1016/j.cca.2008.12.012
• 发表时间: 2009-04-01
• 期刊: CLINICA CHIMICA ACTA
• 影响因子: 5
• 作者: Miwa, Kenji;Inazu, Akihiro;Yamagishi, Masakazu
• 通讯作者: Yamagishi, Masakazu

Impact of the LDL-receptor-related molecules on the achievement of optimal LDL cholesterol level : Evidence from newly identified gene mutations

LDL 受体相关分子对实现最佳 LDL 胆固醇水平的影响：来自新发现的基因突变的证据

• 发表时间: 2010
• 作者: 川尻剛照;多田隼人;中西千明;山岸正和;野口徹;野原淳;小林淳二;馬渕宏;池脇克則
• 通讯作者: 池脇克則

The effects of combination therapy with permitted maximum doses of rosuvastatin, ezetimibe and colestimide in patients with heterozygous familial hypercholesterolemia

瑞舒伐他汀、依折麦布和考来司胺最大允许剂量联合治疗杂合子家族性高胆固醇血症的效果

• 发表时间: 2010
• 作者: Morisaki T;et al;川尻剛照
• 通讯作者: 川尻剛照

Impaired LDL catabolism and increased VLDL and VLDL remnant production in homozygous familial hypercholesterolemia with PCSK9 gene mutation

PCSK9 基因突变的纯合子家族性高胆固醇血症中 LDL 分解代谢受损以及 VLDL 和 VLDL 残余物产生增加

• 发表时间: 2011
• 作者: 川尻剛照,池脇克則,野口徹;ほか
• 通讯作者: ほか

分子予防環境医学(共著) 動脈硬化症

分子预防环境医学（合著者）动脉硬化

• 发表时间: 2010
• 作者: 川尻剛照;山岸正和
• 通讯作者: 山岸正和