| Project/Area Number |
15K09118
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野原 淳 金沢大学, 保健管理センター, 助教 (50313648)
多田 隼人 金沢大学, 附属病院, 助教 (90623653)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 高比重リポ蛋白 / 動脈硬化 / 全エクソームシーケンス |
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| Outline of Final Research Achievements |
The causal genes of 2 cases with extreme hypo-HDL-cholesterolemia (2mg/dL, 6mg/dL) and single case with extreme hyper-HDL-cholesterolemia (170mg/dL) were analyzed by whole exome sequencing. The causes of both of hypo-HDL-cholesterolemia were compound heterozygosity of ABCA1 gene (c.6230C>A/c.6137G>A and c.2842G>A/c.1130C>T). The potential causal gene of the extreme hyper-HDL-cholesterolemia supposed to be "molecule X". The gene was introduced into HEK293 cells. The cholesterol efflux capacity of "molecule X" was not different from that of controls, which suggested the hyper-HDL-cholesterolemia of this index case was not due to increased cholesterol efflux capacity.
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| Academic Significance and Societal Importance of the Research Achievements |
HDLコレステロールは俗に善玉コレステロールと呼ばれ、動脈硬化抑制的と考えられている。著明な低HDLコレステロール血症と高HDLコレステロール血症の原因遺伝子を、全エクソームシーケンス法という新しい手法を用いて検討した。前者は既報のABCA1遺伝子異常であることが比較的短期間で判明し、特に潜性遺伝性疾患の遺伝子解析に有益な手法と考えられる。高HDLコレステロール血症の原因遺伝子は新規の分子であることが想定された。そのメカニズムは、コレステロール引き抜き能亢進によらない可能性が示唆された。
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