Analysis of Locus for Autosomal Dominant Hyperlipidemia

常染色体显性遗传性高脂血症基因座分析

• 批准号: 61571088
• 负责人: HAMAGUCHI Hideo
• 金额: $ 1.54万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61571088/
• 关键词: Autosomal dominant inheritance; Hypercholesterolemia; Gene analysis; LDL receptor; Apolipoprotein B; Apolipoprotein AI; Apolipoprotein E; 家族性高コレステロール血症; 高脂血症; 優性遺伝性高コレステロール血症; LDLレセプター遺伝子; アポリポタンパクAI遺伝子; アポリポタンパクC【III】遺伝子; DNA多型; RFLPs

In order to examine the relationship between autosomal dominant hyperlipidemia and loci, gene for LDL receptor, apolipoprotein B, apolipoprotein E, and apolipoprotein AI were analyzed on hyperlipidemic individuals and their family members. The data obtained in this study indicate that the orgin of mutations of the LDL receptor gene tends to very among defferent families with familial hypercholesterolemia and that the analysis of RFLPs for the LDL receptor gene in family members is useful for the gene diagnosis of familial hypercholesterolemia. In addition, our date indicate that autosomal dominant hypercholesterolemia associated with tendon xanthomas is genetically divided into two groups, that is, the one due to the mutant LDL receptor gene and the other due to mutantions in the locus except the LDL receptor locus. It is important to clarify whether the mutation in the apolipoprotein B gene results in autosomal dominant hypercholesterolemia associated with tendon xanthomas. Besides the results described above, our date also suggest the following: 1) Apolipoprotein E4 is associated with hypercholesterolemia in Japanese living in large cities. 2) S2 allele of apolipoprotein AI RFLPs is not associate with myocardial infarction in Japanese. 3) Familial combined hyperlipidemia is also common in Japanese.

为探讨常染色体显性遗传性高脂血症与基因座的关系，对高脂血症个体及其家系成员的低密度脂蛋白受体、载脂蛋白B、载脂蛋白E和载脂蛋白AI基因进行了分析。本研究结果表明，家族性高胆固醇血症家系低密度脂蛋白受体基因突变的来源不同，家族性高胆固醇血症家系成员低密度脂蛋白受体基因的RFLP分析有助于家族性高胆固醇血症的基因诊断。此外，我们的数据表明，常染色体显性遗传性高胆固醇血症与肌腱黄色瘤相关，遗传上分为两组，即一组是由于低密度脂蛋白受体基因突变引起的，另一组是由于除低密度脂蛋白受体基因以外的基因突变所致。弄清载脂蛋白B基因突变是否会导致常染色体显性遗传性高胆固醇血症与肌腱黄瘤相关，这一点很重要。除上述结果外，我们的研究结果还表明：1)在大城市生活的日本人中，载脂蛋白E4与高胆固醇血症有关。2)日本人载脂蛋白AI RFLPs的S2等位基因与心肌梗死无关。3)家族性混合性高脂血症在日本人中也很常见。

项目成果

Shigeru Tsuchiya: Japanese Journal of Human Genetics. 32. 283-289 (1987)

土屋茂：日本人类遗传学杂志。

Kimiko Yamakawa et. al.: "Taq I Polymorphism in the Human LDL Receptor Gene" Nucleid Acids Research. 15. 7659 (1987)

山川公子等。

Juichi Satoh et.al.: Jpn.J.Human Genet.32. (1987)

Juichi Satoh 等人：Jpn.J.Human Genet.32。

Kimiko Yamakawa: Human Genetics.

山川公子：人类遗传学。

Kimiko Yamakawa et.al.: "Taq I Polymorphism in the LDL Receptor Gene and a Taq I 1.5 kb Band Associated with Familial Hypercholesterolemia" Human Genetics.

Kimiko Yamakawa 等人：“LDL 受体基因中的 Taq I 多态性和与家族性高胆固醇血症相关的 Taq I 1.5 kb 带”人类遗传学。