2007 Fiscal Year Final Research Report Summary
Molecular genetic studies on metabolic syndrome
| Project/Area Number |
17590951
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Okinaka Memorial Institute for Medical Research |
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Principal Investigator |
MINORU Okubo Okinaka Memorial Institute for Medical Research, Investigator (60241238)
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| Co-Investigator(Kenkyū-buntansha) |
EBARA Tetsu Okinaka Memorial Institute for Medical Research, Investigator (40307004)
MURASE Tsoshio Okinaka Memorial Institute for Medical Research, 研究員 (60107612)
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| Project Period (FY) |
2005 – 2007
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| Keywords | genetics / internal medicine / linids / metabolic syndrome / LPL / HL / atherosclerosis |
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| Research Abstract |
Metabolic syndrome (MS) consists of visceral obesity, hypertension, glucose intolerance, and abnormal lipid metabolism, leading to ischemic heart disease (CHD). In this study, we investigated mechanisms aggravating metabolic syndrome through (1) low density lipoprotein related protein 5 (LRP5) and (2) lipoprotein lipase (LPL) and hepatic triglyceride lipase (HL).
(1) We compared allele frequencies of six single nucleotide polymorphisms (SNPs) [Q89R (a/g), N740N (c/t), IVS10+6 (tic), V1119V (a/g), IVS17-30 (g/a), and A1330V (c/t)] between the MS group (n=74) and the control group (n=172). As for IVS17-30, the frequency of minor allele (a) was significantly higher in the MS group. On the other hand, there were no differences in allele frequencies of Q89R and A1330V, which substituted amino acids. Moreover, no differences were found in other SNPs. It remained to be clarified whether IVS17-30 (g/a) polymorphism could be directly associated with the onset or progression of MS, or indirectly through another unknown LRP5 mutations which had linkage disequilibrium with IVS17-30 SNP.
(2) We studied hypertriglyceridemia patients and found a case with a large deletion in the LPL gene caused by Alu transposons, a case with inactive mutant LPL proteins, and a case with reduced HL activity. In addition, we found a case with metabolic cardiomyopathy resulted from a nonsense mutation in the AGL gene. Furthermore, we showed high prevalence of CHO in patients with high Lp (a) levels.
These results suggested that various factors were associated with the onset of MS.
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