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

• Project/Area Number: 14572140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: University of Shizuoka (2003); University of Tsukuba (2002)
• Principal Investigator: KOBAYASHI Kimiko Univ. of Shizuoka, School of Food and Nutritional Sciences, Associate Professor, 食品栄養科学部, 助教授 (90215319)
• Co-Investigator(Kenkyū-buntansha): YANAGI Hisako Univ.of Tsukuba, institute of community Medicine, Associate Professor, 社会医学系, 助教授 (10241811)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: Quantitative-trait-locus / genome-wide linkage search / hypercholesterolemia / hypoalphalipoproteinemia / 脂質代謝異常 / QTL連鎖解析

Research Abstract

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.

Research Products

• [Publications] Yamakawa-Koabayashi et al.: "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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Endo K et al.: "Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum tryglyceride level in Japanese schoolchildren."Hum. Genet.. 111. 570-572 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamakawa-Kobaashi K et al.: "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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Watanabe H et al.: "Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia."Proteomics. 4. 537-543 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Endo K, Yanagi H, Araki J, Hirano C, Yamakawa-Kobayashi K, Tomura S.: "Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren."Hum.Genet.. 111. 570-572 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamakawa-Kobayashi K, Yanagi H, Yu Y, Endo K, Arinami T, Hamaguchi H.: "Associations 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Watanabe H, Hamada H, Yamada N, Sohda S, Yamakawa-Kobayashi K, Yoshikawa H, Arinami T: "Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia."Proteomics. 4. 537-543 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamakawa-Kobayashi K et al.: "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)
• [Publications] Yamakawa-Kobayashi K et al.: "Associations between serum high-density lipoprotein cholesterol or apolipoproteinA1 levels and common genetic variants of the ABCA1 gene in Japanese school-aged children."Metabolism. 53. 182-186 (2004)
• [Publications] Yamakawa-Kobayashi K, et al.: "A Val227Ala polymorphism in the peroxisome proliferator activated receptor α (PPARα) gene is associated with variations of serum lipids levels"J. Med. Genet.. 39. 189-191 (2002)
• [Publications] 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)
• [Publications] Endo K, et al.: "Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren"Human Genetics. 111. 570-572 (2002)