Whole genome association study on type 2 diabetes susceptibility genes using microsatellite markers and DNA pool

• Project/Area Number: 14571096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Ehime University
• Principal Investigator: MAKINO Hideichi Ehime University, School of Medicine, Laboratory medicine, Professor, 医学部, 教授 (50009578)
• Co-Investigator(Kenkyū-buntansha): ONUMA Hiroshi Ehime University, School of Medicine, Laboratory medicine, Instructor, 医学部, 助手 (00294794) ; OSAWA Haruhiko Ehime University, School of Medicine, Laboratory medicine, Associate Professor, 医学部, 助教授 (90294800)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥2,800,000 (Direct Cost: ¥2,800,000); Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: Diabetes / Susceptibility gene / SNP / Polymorphisms / Haplotype

Research Abstract

To prevent the onset of type 2 diabetes, it is required to identify its susceptibility genes. We initially planned to employ microsatellite markers throughout the whole genome and each DNA pool of cases or controls for the whole genome association study, and established a reproducible system. It has been turned out that the diabetes team in the millennium project we belong to are also doing the whole genome association study using SNPs and microsatellite markers. Since this progress is faster than expected, we have decided to start fine mapping after the candidate loci have been identified by this project. In parallel, we analyzed candidate gene for insulin resistance seen with type 2 diabetes such as FOXC2, phosphodiesterase 3 B(PDE3B), and resistin. We analyzed〜1kb of the 5' flanking region and the coding region of the FOXC2 gene, and identified three frequent SNPs and four frequent haplotypes defined by them. Neither of them was associated with type 2 diabetes. We also analyzed the 〜1kb of the 5' flanking region of the PDE3B gene along with a frequent SNP+1389G>A, but no association with type 2 diabetes was evident. We also found that the frequent SNP+299G>A of the resistin was not associated with type 2 diabetes even in combination with frequent SNPs of genes critical for lipid metabolism. Therefore, frequent SNPs analyzed in FOXC2, PDE3B, and rsistin are unlikely to have major effects on susceptibility to type 2 diabetes.

Research Products

• [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the 5' flanking region of the human phosphodiesterase 3B gene : Absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes."Mol Genet Metab. 79. 43-51 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the FOXC2 gene : The absence of evidence for the association of three frequent SNPs and four common haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ochi, M. et al.: "The absence of evidence for major effects of the frequent SNP 299G>A in the resistin gene on susceptibility to insulin resistance syndrome associated with Japanese type 2 diabetes."Diabetes Res Clin Pract. 61. 191-198 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Osawa H. et al.: "Systematic search for single nucleotide polymorphisms in the FOXC2 gene : The absence of evidence for the association of three frequent single nucleotide polymorphisms and four common haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Osawa H. et al.: "Systematic search for single nucleotide polymorphisms in the 5' flanking region of the human phosphodiesterase 3B gene : Absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes."Mol Genet Metab. 79. 43-51 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ochi, M. et al.: "The absence of evidence for major effects of the frequent SNP 299G>A in the resistin gene on susceptibility to insulin resistance syndrome associated with Japanese type 2 diabetes."Diabetes Res Clin Pract. 61. 191-198 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the 5' flanking region of the human phosphodiesterase 3B gene : Absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes."Mol Genet Metab. 79. 43-51 (2003)
• [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the FOXC2 gene : The absence of evidence for the association of three frequent SNPs and fourcommon haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)
• [Publications] Ochi, M. et al.: "The absence of evidence for major effects of the frequent SNP 299G>A in the resistin gene on susceptibility to insulin resistance syndrome associated with Japanese type 2 diabetes."Diabetes Res Clin Pract. 61. 191-198 (2003)
• [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisrns (SNPs) in the 5'flanking region of the human phosphodiesierase 3B gene: Absence of evidence for major effects of identified polymorphisms on susceptib ility to Japanese type 2 diabetes"Mol Genet Metab. (発売予定). (2003)
• [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the FOXC2 gene: The absence of ev idence for the association of three frequent SNPs and four common haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)