| Project/Area Number |
05454327
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Yamagata Universtity |
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Principal Investigator |
ICHINOSE Akitada Yamagata University, School of Medicine, Professor., 医学部, 教授 (10241689)
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| Co-Investigator(Kenkyū-buntansha) |
IZUMI Tomonori Yamagata University, School of Medicine, Instructor., 医学部, 助手 (00261694)
橋口 照人 山形大学, 医学部, 助手 (70250917)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | lipoprotein (a) / apolipoprotein (a) / atherosclerosis / thrombosis / regulatory region / transcriptional activity / genetic polymorphisms / genetic diagnosis / プラスミノゲン / クリングルドメイン / 高脂血症 |
|---|
| Research Abstract |
Concentration of lipoprotein (a) in plasma is inherited in an autosomal codominant manner and its high concentration leads to atherothrombotic disease. Nucleotide sequence analysis of the apolipoprotein (a) gene revealed the presence of polymorphisms in its 5'-flanking region, which can be analyzed by in vitro amplification employing gene-specific primers. Genomic DNAs from normal individuals have been subclassified into four alleles according to the patterns of restriction digestion. The ratios of these subtypes differed between Caucasians and Japanese, and in patients with myocardial infarction. The differences in the nucleotide sequence of the 5'-regulatory region may lead to differential transcriptional efficiency, which in turn results in a wide variety of plasma Lp (a) levels, not only among individuals but also between ethnic groups. This hypothesis was confirmed by the CAT (chloramphenicol acethyltransferase) assay when each of the four types of 5'-alleles had been inserted into a promoterless CAT vector and its transcriptional activity had been compared directly. There was 3-fold difference in transcriptional activities between the highest type C and the lowest type D when the activity of type A was defined as 100%. These results will contribute to understanding of molecular mechanisms of atherothrombotic disease, and to development of genetic diagnosis and treatment of hyperlipoprotein (a) emia in the near future.
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