Identification of the susceptive genes for hypercholesterolemia and hypoalphalipoproteinemia by Genome-wide linkage analysis

通过全基因组连锁分析鉴定高胆固醇血症和低α脂蛋白血症的易感基因

• 批准号: 14572140
• 负责人: KOBAYASHI Kimiko
• 金额: $ 1.92万
• 依托单位: University of Shizuoka (2003)University of Tsukuba (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14572140/
• 关键词: Quantitative-trait-locus; genome-wide linkage search; hypercholesterolemia; hypoalphalipoproteinemia; 脂質代謝異常; QTL連鎖解析

We conducted a genome-wide linkage search for susceptibility gene influencing interindividual variation in serum lipid levels in a Japanese population. We have analyzed genotypic data of 352 microsatellite markers in 43 Japanese families (172 members) of probands with hypercholesterolemia. Quantitative-trait-locus (QTL) analysis for serum lipid levels was carried out by a Haseman-Elston method. We have observed significant LOD scores for the linkage of serum total cholesterol level on D3S1580, D11S935, and D15S120. In addition, we have observed significant in another 32 Japanese families (138 members). Only the linkage between serum total cholesterol level and D3S1580 have been ascertained. These data suggest that the chromosomal region around D3S1580 may be a susceptibility region influencing variation in total cholesterol level. Further investigation will be necessary to identify and test plausible candidate genes for hypercholesterolemia and hypoalphalipoproteinemia in this region.

我们对影响日本人群血脂水平个体间差异的易感基因进行了全基因组连锁搜索。我们分析了43个高胆固醇血症日本家系(172名成员)的352个微卫星标记的基因分型数据。用Haseman-Elston方法进行血脂水平的QTL分析。我们观察到D3S1580、D11S935和D15S120上的血清总胆固醇水平连锁的显著LOD得分。此外，我们在另外32个日本家庭(138个成员)中观察到显著的差异。只有血清总胆固醇水平与D3S1580之间的联系已被确定。这些数据提示D3S1580附近的染色体区域可能是影响总胆固醇水平变化的易感区域。有必要进行进一步的研究，以确定和测试该地区高胆固醇血症和低脂蛋白血症的合理候选基因。

项目成果

Yamakawa-Kobayashi K, Ishiguro H, Arinami T, Miyazaki R, Hamaguchi H.: "A Val227Ala polymorphism in the peroxisome proliferators activated receptor α(PPARA) gene is associated with variations in serum lipids levels."J.Med.Genet.. 39. 189-191 (2002)

Yamakawa-Kobayashi K、Ishiguro H、Arinami T、Miyazaki R、Hamaguchi H.：“过氧化物酶体增殖物激活受体 α (PPARA) 基因中的 Val227Ala 多态性与血清脂质水平的变化相关。”J.Med.Genet.. 39. 189-191 (2002)

Yamakawa-Kobayashi K, et al.: "Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL an LDL cholesterol levels in postmenopausal women under hormone replacement therapy"Atheroscierosis. 162. 17-21 (2002)

Yamakawa-Kobayashi K 等人：“激素替代疗法下绝经后妇女肝脂肪酶基因中的 -514C/T 多态性与血清 HDL 和 LDL 胆固醇水平的关系”动脉粥样硬化。

Watanabe H et al.: "Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia."Proteomics. 4. 537-543 (2004)

Watanabe H 等人：“蛋白质组分析显示先兆子痫患者的血清凝聚素水平升高。”蛋白质组学。

Yamakawa-Kobayashi K, Yanagi H, Endo K, Arinami T, Hamaguchi H.: "Relationship between serum HDL-C levels and common genetic variants of the endothelial lipase gene in Japanese school-aged children."Hum.Genet.. 113. 311-315 (2003)

Yamakawa-Kobayashi K、Yanagi H、Endo K、Arinami T、Hamaguchi H.：“日本学龄儿童血清 HDL-C 水平与内皮脂肪酶基因常见遗传变异之间的关系。”Hum.Genet.. 113。

Yamakawa-Kobayashi K et al.: "Assocations between serum high-density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA1 gene in Japanese school-aged children."Metabolism. 53. 182-186 (2004)

Yamakawa-Kobayashi K 等人：“日本学龄儿童血清高密度脂蛋白胆固醇或载脂蛋白 AI 水平与 ABCA1 基因常见遗传变异之间的关联。”代谢。