Genetic analysis of lipid related genes in patients with hypertriglyceridemia and low HDL cholesterolemia

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Fukuoka University
• Principal Investigator: MATSUNAGA AKIRA 福岡大学, 医学部, 教授 (60221587)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 高トリグリセライド血症 / 低HDLコレステロール血症 / 遺伝子解析 / 次世代シーケンサー

Outline of Final Research Achievements

The primary goal was to clarify the genetic factors affecting dyslipidemia in Japan. Exome analysis was performed on 23 cases whose serum triglyceride (TG) level exceeded 1000 mg/dL at Fukuoka University Hospital. Genetic analysis of 49 genes that have been reported to be associated with serum TG levels was performed. In this analysis, four novel mutations, APOB(p.I4533L), MLXIPL(p.M490I),NCAN(p.L152M) and TIMD4(p.S264T) were found. Furthermore, according to previous reports and algorithm analysis, it was suggested that GPIHBP1 (p.C14F), APOA5 (p.T184S; p.G185C), APOE (p.E262K, p.E263K), GCKR (p.V103M; c.354 + 1G> A; p.P446L), LMF1 (p.M159V; p.G410R), MLXIPL (p.Q241H) and LRP1 (p.G813R; p.R2173Q2; p.AN4054L2) were part of the causes of hypertriglyceridemia. The genetic analysis of hypo-HDL-cholesterolemia four cases including severe low HDL-cholesterolemia was performed. We found ABCA1 deficiency due to homozygous mutation p.V635fsX658 from one case of severe hypo-HDL-cholesterolemia.

Free Research Field

脂質異常症、動脈硬化

Academic Significance and Societal Importance of the Research Achievements

脂質異常症の原因遺伝子検索は世界中で行われている。しかし、遺伝子変異による影響は人種や地域による偏りも大きいと考えられている。今回我々は成人の日本人を対象として、主に重症の高トリグリセライド血症および低HDLコレステロール血症の遺伝子解析をおこなった。特に重症高トリグリセライド血症については、49遺伝子について詳細なエクソーム解析を行うことができ、貴重なデータを得た。重症低HDL-C血症の1例よりABCA1遺伝子変異p.V635fsX658のホモ接合体変異によるABCA1欠損症を見出した。