| Project/Area Number |
14572198
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
MIYAKE Yasuko National Cardiovascular Center Research Institute, Dept.Etiology & Pathophysiology, Research Head, 病因部, 室長 (00132936)
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| Co-Investigator(Kenkyū-buntansha) |
山村 卓 国立循環器病センター研究所, 病因部, 室長 (20132938)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | LDL receptor / common mutation / familial hypercholesterolemia / variety of mutations / gene diagnosis / genetic basis of hypercholesterolemia / 高脂血症の遺伝素因 / 高頻度変異 / 表現形 / mild type変異 |
|---|
| Research Abstract |
Mutations in the low density lipoprotein(LDL) receptor gene are responsible for familial hypercholesterolemia(FH). At present, more than 600 mutations in the LDL receptor gene are known to underlie FH. However the arrays of mutations are known to vary in different populations. Japanese people are uniracial and Japan has been isolated geographically and politically for more than a thousand years, therefore existence of limited kinds of mutations is expected in this country.
Mutation analyses by PCR-SSCP and Southern blotting were conducted in 207 unrelated patients who were clinically diagnosed as FH heterozygotes. Half of them, were born in the Kansai district. The 56 different LDL receptor gene mutations were characterized. The eight relatively common mutations were responsible for 32% of our FH cases. The eight common mutations are C317S(6.3%), K790X(6.3%), 1845+2T→C(6.3%), L547V(3.4%), P664L(2.9%), D412H(2.4%), 2313→3C→A(2.4%) and V776M(2.4%). P664L is a recurrent mutation but the others are specific to Japanese population.
The remaining 48 mutations were only encountered in a single to 3 cases. These minor mutations comprised 26% of the cases analyzed.
From the analyses of molecular phenotypes and clinical features, the clinical phenotypes reflect well the type of mutations.
These results showed that there are vast varieties in the LDL receptor mutations in Japanese FH, thus, in general, the gene diagnosis ofFH seems to be diffic
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