Analysis of additive effects of common functional variants of candidate genes on the risk for coronary artery diseases

• Project/Area Number: 12672197
• 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 Tsukuba
• Principal Investigator: KOBAYASHI Kimiko Institute of Basic Medical Sciences, University of Tsukuba, Assistant Professor, 基礎医学系, 講師 (90215319)
• Co-Investigator(Kenkyū-buntansha): HAMAGUCHI Hideo Institute of Basic Medical Sciences, University of Tsukuba, Professor, 基礎医学系, 教授 (00091918)
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: coronary artery diseases / multifactorial disease / additive effects / 機能性変異遺伝子 / 脂質代謝異常

Research Abstract

Coronary artery disease (CAD) is a common multifactorial disease. Dyslipidemia and hypertension are important risk factor for CAD. At first we have screened the common functional variants in the candidate genes for dyslipidemia and hypertension. We have found that a Val227Ala polymorphism in peroxisome proliferator activated receptor α gene is associated with variations in serum lipid levels, and a Lys528Arg polymorphism in adipocyte-derived leucine aminopeptidase gene is associated with blood pressure. But we could not found the associations between such polymorphisms and CAD.
Furthermore, we have investigated the relationship between the functional variants of 11 candidate genes for CAD (APOE, MTHFR, AGT, ACE, LPA, HTT, LIPC, ADRB3, LPL, PAI1, ENOS) and CAD. Among of them, the significant associations with CAD were observed in the variants of APOE, LPA, and MTHFR. Additive effects of the variants of these three genes on the risk for CAD were investigated. The odds ratio for the risk of CAD associated with each variant ranged from 1.4 to 1.9. The odds ratio associated with the presence of two variant genes were 3.5. These data suggest that combined and additive effects of common functional variants of several candidate genes may be an important genetic factor for CAD.

Research Products

• [Publications] N.Yamamoto, et al.: "Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension"Hum. Mutat.. 19. 251-257 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Yamakawa-Kobayashi, et al.: "A Val227Ala polymorphism in the peroxisome proliferator activated receptor a (PPAR a) gene is associated with variations of serum lipids levels"J. Med. Genet.. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Yamakawa-Kobayashi, et al.: "Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy"Atherosclerosis. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamakawa-Kobayashi K, Arinami T, Hamaguchi H et al.: "A Val227Ala polymorphism in the peroxisome proliferator activated receptor α (PPAR α) gene is associated with variations of serum lipids levels"J. Med. Genet.. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamakawa-Kobayashi K, Arinami T, Hamaguchi H et al.: "Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy"Atherosclerosis. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamamoto N, Yamakawa-Kobayashi K, Hamaguchi H et al.: "Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension"Hum. Mutat.. 19. 251-257 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [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.. (印刷中).
• [Publications] Yamakawa-Kobayashi K et al.: "Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy"Atherosclerosis. (印刷中).
• [Publications] Yokouchi Y et al.: "A Significant Evidence for Linkage of Mite-Sensitive Childhood Asthma to Chromosome 5q31-q33 nearthe Interleukin 12 B Locus by A Genome-wide Search in Japanese families."Genomics. 66. 152-160 (2000)
• [Publications] Noguchi E et al.: "Mutation screening of Interferon regulatory factor l gene (IRF-l) as a candidate gen for a sthma."Clin Exp Allergy. 30. 1563-1567 (2000)
• [Publications] Ohtsuki T et al.: "Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia."Mol Psychatry. in press.
• [Publications] Yamada N et al.: "The 4G/5G polymorphism of the plasminogen activator inhibitor-l gene is associated with severe preeclampsia"J Hum Genet. 45. 138-141 (2000)