Analysis of genes causing autosomal dominant hypercholesterolemia

常染色体显性高胆固醇血症的基因分析

• 批准号: 63571084
• 负责人: HAMAGUCHI Hideo
• 金额: $ 1.34万
• 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: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63571084/
• 关键词: hypercholesterolemia; autosomal dominant hypercholesterolemia; LDL receptor gene; apolipoprotein B gene; familial hypercholesterolemia; familial combined hyperlipoproteinemia; familial defective apolipoprotein B-100; 遺伝性高コレステロ-ル血症; アキレス腱肥厚; 高コレステ

To clarify genetic causes of autosomal dominant hypercholesterolemia, pedigree analysis of genes encoding LDL receptor and apolipoprotein B were performed in families with hereditary hypercholesterolemia. In all 17 families with probands having relatively severe hypercholesterolemia (cholesterol levels 300- 450 mg/dl) associated with Achilles tendon xanthomas, relatively severe . hypercholesterolemia was linked with a partial deletion, an abnormal TaqI band, or RFLP of the LDL receptor gene, indicating that most of, if not all, the relatively severe hypercholesterolemia associated with Achilles tendon xanthomas is caused by a defective LDL receptor gene. On the other hand, only two families seemed to be classic familial hypercholesterolemia in ten families with hereditary hypercholesterolemia which were selected by family studies following school surveys. Moderate hereditary hypercholesterolemia was observed in the remaining eight families. Among the eight families, the LDL receptor gene RFLP was linked with hypercholesterolemia in two families and clinical,features of familial combined hyperlipoproteinemia were observed in another two families. No linkage relationship was observed between LDL receptor gene RFLP and hypercholesterolemia in three of the other four families. The gene for familial defective apolipoprotein B-100 was not detected in these families. These data suggest that moderate hereditary hypercholesterolemia is more common than classic familial hypercholesterolemia and that many of moderate hereditary hypercholesterolemia may be caused by a defective gene at the loci distinct from the LDL receptor gene.

为了阐明常染色体显性高胆固醇血症的遗传原因，对遗传性高胆固醇血症家族进行了低密度脂蛋白受体和载脂蛋白B编码基因的家系分析。在所有17个先证家族中，有相对严重的高胆固醇血症（胆固醇水平300- 450 mg/dl）与跟腱黄瘤相关，相对严重。高胆固醇血症与低密度脂蛋白受体基因的部分缺失、TaqI条带异常或RFLP有关，这表明大多数（如果不是全部）与跟腱黄瘤相关的相对严重的高胆固醇血症是由缺陷的低密度脂蛋白受体基因引起的。另一方面，在学校调查后通过家庭研究选择的10个遗传性高胆固醇血症家庭中，只有2个家庭似乎是典型的家族性高胆固醇血症。在其余8个家族中观察到中度遗传性高胆固醇血症。在8个家族中，LDL受体基因RFLP与2个家族高胆固醇血症相关，另外2个家族出现家族性合并高脂蛋白血症的临床特征。LDL受体基因RFLP与其他4个家族中3个家族的高胆固醇血症无连锁关系。在这些家族中未检测到家族性载脂蛋白B-100缺陷基因。这些数据表明，中度遗传性高胆固醇血症比典型家族性高胆固醇血症更为常见，许多中度遗传性高胆固醇血症可能是由与LDL受体基因不同的位点上的缺陷基因引起的。

项目成果

K.Yuzawa,et al.: "An ultrasonographic method for detection of Achilles tendon xanthomes in familial hypercholesterolemia" Atherosclerosis. 75. 211-218 (1989)

K.Yuzawa 等人：“用于检测家族性高胆固醇血症中跟腱黄瘤的超声方法”动脉粥样硬化。

K. Yamakawa, et al.: "Family studies of the LDL receptor gene of relatively severe hereditary hypercholesterolemia associated with Achilles tendon xanthomas" Human Genetics.

K. Yamakawa 等人：“与跟腱黄瘤相关的相对严重的遗传性高胆固醇血症的 LDL 受体基因的家庭研究”人类遗传学。

K. Yuzawa, et al.: "An ultrasonographic method for detection of Achilles tendon xanthomas in familial hypercholesterolemia" Atherosclerosis Vol. 75, 211-218 (1989).

K. Yuzawa 等人：“用于检测家族性高胆固醇血症中跟腱黄色瘤的超声检查方法”动脉粥样硬化卷。

T.Arinami,H.Hamaguchi,et al.: "Assignment of the apolipoprotein A-I qene to llq23 based on RFLP in a case with a partial deletion of chromosome 11,del(11)(q23.3→qter)" Human Genetics.

T.Arinami、H.Hamaguchi 等人：“在 11 号染色体部分缺失的情况下，基于 RFLP 将载脂蛋白 A-I qene 分配给 llq23，del(11)(q23.3→qter)”人类遗传学。

K.Yamakawa;T.Okafuji;H.Hamaguchi;et al.: Human Genetics. 80. 1-5 (1988)

K.Yamakawa；T.Okafuji；H.Hamaguchi；等：人类遗传学。