Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Apolipoprotein C-II Deficiency with No Rare Variant in the APOC2 Gene
Satoru TakaseJun-ichi OsugaHayato FujitaKazuo HaraMotohiro SekiyaMasaki IgarashiMikio TakanashiYoshinori TakeuchiYoshihiko IzumidaKeisuke OhtaMasayoshi KumagaiMakiko NishiMidori KubotaYukari MasudaYoshino TairaSachiko OkazakiYoko IizukaNaoya YahagiKen OhashiHiroshi YoshidaHidekatsu YanaiNorio TadaTakanari GotodaShun IshibashiTakashi KadowakiHiroaki Okazaki
著者情報
ジャーナル フリー

2013 年 20 巻 5 号 p. 481-493

詳細
抄録

Aim: Familial apolipoprotein C-II (apoC-II) deficiency is a rare autosomal recessive disorder with marked hypertriglyceridemia resulting from impaired activation of lipoprotein lipase. In most cases of apoC-II deficiency, causative mutations have been found in the protein-coding region of APOC2; 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), which resulted from decreased promoter activity or improper splicing of apoC-II mRNA due to homozygous mutations in APOC2. Here we aim to dissect the molecular bases of a new case of hypoapoC-II.
Methods: We performed detailed biochemical/genetic analyses of our new case of hypoapoC-II, manifesting severe hypertriglyceridemia (plasma triglycerides, 3235 mg·dL-1) with markedly reduced levels of plasma apoC-II (0.6 mg·dL-1).
Results: We took advantage of a monocyte/macrophage culture system to prove that transcription of apoC-II mRNA was decreased in the patient’s cells, which is compatible with the reported features of hypoapoC-II. Concomitantly, transcriptional activity of the minigene reporter construct of the patient’s APOC2 gene was decreased; however, no rare variant was detected in the patient’s APOC2 gene. Fifty single nucleotide variants were detected in the patient’s APOC2, but all were common variants (allele frequencies >35%) that are supposedly not causative.
Conclusions: A case of apoC-II deficiency was found that is phenotypically identical to hypoapoC-II but with no causative mutations in APOC2, implying that other genes regulate apoC-II levels. The clinical entity of hypoapoC-II is discussed.

著者関連情報

この記事はクリエイティブ・コモンズ [表示 - 非営利 - 継承 4.0 国際]ライセンスの下に提供されています。
https://creativecommons.org/licenses/by-nc-sa/4.0/deed.ja
前の記事 次の記事
feedback
Top