2021 Fiscal Year Final Research Report
Genetic Analysis of Familial Hypercholesterolemia using Whole-exome Sequence
| Project/Area Number |
19K08553
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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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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
下島 正也 金沢大学, 附属病院, 特任助教 (00613754)
多田 隼人 金沢大学, 附属病院, 助教 (90623653)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 家族性高コレステロール血症 / 網羅的遺伝子解析 / 遺伝子多型 |
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| Outline of Final Research Achievements |
Familial hypercholesterolemia (FH) is used to be recognized as a simple autosomal dominant monogenic dosorder caused by low-density lipoprotein receptor gene mutation. Recently, it has been recognized the pathophysiology of polygenic FH; an accumulation of common small-effect-sized variants in a single individual.
We recruited and genotyped clinically diagnosed FH (CDFH) patients from the Kanazawa University FH registry and controls from the Shikamachi Health Improvement Practice genome cohort. We calculated PRS from 3.6 million variants of each participant for LDL-C (PRSLDLC) using a genome-wide association study summary statistic from the BioBank Japan Project. We tested a total of 1223 participants for the analyses. PRSLDLC was significantly higher in mutation negative CDFH patients than in controls. PRSLDLC was also significantly linked to LDL-C in controls but not in FH patients. However, PRSLDLC may have little additional effect on LDL-C and CAD among FH patients.
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| Free Research Field |
循環器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
家族性高コレステロール血症（FH）は従来、低比重リポ蛋白受容体遺伝子変異を主な原因とする単純な優（顕）性遺伝性疾患であると考えられていた。しかしながら、臨床的にFHと診断される症例の1/3～1/4の原因遺伝子を同定できないことが知られている。これらの集団の中に「多遺伝子FH」が存在するとの発想から研究を開始した。しかしながら、多遺伝子リスクスコアはLDL-C値と有意に相関したものの、冠動脈疾患と相関せず、多遺伝子FHと診断できる症例もなかった。原因遺伝子を同定できないFHの発症には、今回の検討で明確にできなかった遺伝的背景か環境因子が影響している可能性が考えられた。
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