IDENTIFICATION OF SITOSTEROLEMIA LOCUS BY LINKAGE ANALYSES

通过连锁分析鉴定谷甾醇基因座

• 批准号: 10671064
• 负责人: KOJIMA Hideto
• 金额: $ 2.11万
• 依托单位: SHIGA UNIVERSITY OF MEDICAL SCIENCE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671064/
• 关键词: sitosterolemia; cholesterol; xanthoma; atherosclerosis; plant sterol; sitosterol; campesterol; diabetes mellitus; 動脈硬化症; 植物コレステロール; 遺伝子

Sitosterolemia is a rare lipid disorder characterized by the presence of tendon and tuberous xanthomas, premature atherosclerotic disease, absence of a family history of premature coronary artery disease. Patients suffering form this disease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Identification of this gene defect may therefore throw light on regulation of net dietary cholesterol absorption and lead to advancement in the management of this important cardiovascular risk factor. Therefore, we performed (1) mapping a gene of sitosterolemia locus in subjects with sitosterolemia, and (2) Identification of sitosterolemia gene related products in diabetes mellitus, another common disease that shows plasma high plant sterol levels. By studying 10 well-characterized families with sitosterolemia, we have localized the genetic defect to chromosome 2p21, between microsatellite markers D2S1352. By studying diabetic patients, model animals, and intestinal cell line, we observed that insulin-deficient state leads to the increased intestinal plant sterol absorption, and that this abnormality is related to the intestinal cell growth and differentiation. We are now continuing the further studies on these 2 important themes.

谷甾醇血症是一种罕见的脂质紊乱，其特征是存在肌腱和结节性黄色瘤、过早的动脉粥样硬化性疾病、缺乏过早的冠状动脉疾病家族史。患有这种疾病的患者似乎从肠道过度吸收胆固醇和植物甾醇。因此，这种基因缺陷的鉴定可能会揭示净膳食胆固醇吸收的调节，并导致这一重要的心血管危险因素的管理进展。因此，我们进行了（1）在患有谷甾醇血症的受试者中定位谷甾醇血症基因座的基因，和（2）在糖尿病（显示血浆高植物甾醇水平的另一种常见疾病）中鉴定谷甾醇血症基因相关产物。通过对10个谷甾醇血症家系的研究，我们将遗传缺陷定位于染色体2p21，位于微卫星标记D2S1352之间。通过对糖尿病患者、模型动物和肠道细胞系的研究，我们观察到胰岛素缺乏状态导致肠道对植物甾醇的吸收增加，这种异常与肠道细胞的生长和分化有关。我们现正继续就这两个重要课题进行进一步研究。

项目成果

Patel S B, Salen G, Hidaka H, et al.: "Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21"J Clin Invest. 102. 5. 1041-1044 (1998)

Patel SB、Salen G、Hidaka H 等人：“绘制了参与调节膳食胆固醇吸收的基因图谱。谷甾醇血症基因座位于染色体 2p21”J Clin Invest。

Kojima H, et al.: "Concerted regulation of early enterocyte differentiation by insulin-like growth factor I, insulin, and transforming growth factor-β1"Proc Assoc Am Physicians. 110. 3. 197-206 (1998)

Kojima H等人：“胰岛素样生长因子I、胰岛素和转化生长因子-β1对早期肠上皮细胞分化的协同调节”Proc Assoc Am Physicians。 110. 3. 197-206 (1998)

Patel S B, Salen G, Hidaka H, et al.: "Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21"J. Clin Invest. 102. 5. 1041-1044 (1998)

Patel SB、Salen G、Hidaka H 等人：“绘制了参与调节膳食胆固醇吸收的基因图谱。谷甾醇血症基因座位于染色体 2p21”，J.

Shailendra B.Patel: "Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21" The Journal of Clinical Investigation. 102巻5号. 1041-1044 (1998)

Shailendra B.Patel：“绘制参与调节膳食胆固醇吸收的基因。谷甾醇血症基因座位于染色体 2p21”，《临床研究杂志》第 102 卷，第 5 期。1041-1044（1998 年）。

Kojima H, et al.: "Effect of glycemic control on plasma plant sterol levels and post-heparin diamine oxidase activity in type 1 diabetic patients"Atherosclerosis. 145. 389-397 (1999)

Kojima H 等人：“血糖控制对 1 型糖尿病患者血浆植物甾醇水平和肝素后二胺氧化酶活性的影响”动脉粥样硬化。