Molecular Dissection of hypoapoC-II caused by defective mRNA transcription

mRNA转录缺陷引起的hypoapoC-II的分子解剖

• 批准号: 24790914
• 负责人: TAKASE Satoru
• 金额: $ 2.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790914/
• 关键词: chylomicronemia; apoC-II deficiency; SNP; rare variant; アポﾘﾎﾟ蛋白C-II; 高中性脂肪血症; 全ゲノム解析; アポリポ蛋白C-II; リポ蛋白リパーゼ

Familial apolipoprotein C-II (apoC-II) deficiency is a rare autosomal recessive disorder with marked hypertriglyceridemia resulting from impaired activation of LPL. In most cases of apoC-II deficiency, causative mutations have been found in the protein-coding region of APOC2 gene; however, several atypical cases of apoC-II deficiency were reported to have markedly reduced, but detectable levels of plasma apoC-II protein (hereafter referred to as hypoapoC-II). A case of apoC-II deficiency was found that is phenotypically identical to hypoapoC-II. We took advantage of a monocyte/macrophage culture system to prove that transcription of apoC-II mRNA was decreased in the patient's cells. However, all of the fifty single nucleotide variants detected in the patient's APOC2 gene were common variants that are supposedly not causative, implying that other mutations regulate apoC-II levels. Whole-genome sequencing is underway to identify the causative mutation.

家族性载脂蛋白C-Ⅱ（apoC-Ⅱ）缺乏症是一种罕见的常染色体隐性遗传病，由于脂蛋白脂蛋白（LPL）的活化受损而导致显著的高脂血症。在大多数apoC-II缺乏症病例中，在APOC 2基因的蛋白编码区发现了致病突变;然而，据报道，几例apoC-II缺乏症的非典型病例的血浆apoC-II蛋白水平显著降低，但可检测到（下文称为hypoapoC-II）。发现一例apoC-II缺乏症与hypoapoC-II表型相同。我们利用单核细胞/巨噬细胞培养系统证明患者细胞中apoC-II mRNA的转录降低。然而，在患者的APOC 2基因中检测到的所有50个单核苷酸变异都是被认为不是致病性的常见变异，这意味着其他突变调节apoC-II水平。全基因组测序正在进行中，以确定致病突变。

项目成果

蛋白翻訳領域に変異の無い非典型的アポC-II 欠損症の分子生物学的解析

蛋白质翻译区无突变的非典型 apoC-II 缺陷的分子生物学分析

• 发表时间: 2013
• 作者: 高瀬暁;大須賀淳一;藤田逸人;原一雄;高梨幹生;飯塚陽子;吉田博;柳内秀勝;多田紀夫;山田信博;石橋俊;岡崎啓明;門脇孝
• 通讯作者: 門脇孝

Apolipoprotein C-II Deficiency with No Rare Variant in the <i>APOC2</i> Gene

载脂蛋白 C-II 缺陷且 <i>APOC2</i> 基因无罕见变异

• DOI: 10.5551/jat.16592
• 发表时间: 2013
• 期刊: Journal of Atherosclerosis and Thrombosis
• 影响因子: 4.4
• 作者: Takase S;Osuga J;Fujita H;Hara K;Sekiya M;Igarashi M;Takanashi M;Takeuchi Y;Izumida Y;Ohta K;Kumagai M;Nishi M;Kubota M;Masuda Y;Taira Y;Okazaki S;Iizuka Y;Yahagi N;Ohashi K;Yoshida H;Yanai H;Tada N;Gotoda T;Ishibashi S;Kadowaki T,
• 通讯作者: Kadowaki T,

蛋白翻訳領域に変異の無いapoC-II欠損/低下症の分子生物学的解析

蛋白质翻译区无突变的 apoC-II 缺陷/视力减退的分子生物学分析

• 发表时间: 2013
• 作者: 高瀬暁;大須賀淳一;藤田逸人;原一雄;高梨幹生;泉田欣彦;久保田みどり;升田紫;飯塚陽子;吉田博;柳内秀勝;多田紀夫;山田信博;石橋俊;岡崎啓明;門脇孝
• 通讯作者: 門脇孝

Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene.

载脂蛋白 C-II 缺陷，APOC2 基因无罕见变异。

• 发表时间: 2013
• 期刊: J. Atheroscler. Thromb.
• 作者: Takase S;Osuga J;Fujita H;Hara K;Sekiya M;Igarashi M;Takanashi M;Takeuchi Y;Izumida Y;Ohta K;Kumagai M;Nishi M;Kubota M;Masuda Y;Taira Y;Okazaki S;Iizuka Y;Yahagi N;Ohashi K;Yoshida H;Yanai H;Tada N;Gotoda T;Ishibashi S;Kadowaki T,
• 通讯作者: Kadowaki T,