2007 Fiscal Year Final Research Report Summary
Molecularr epidemiology about unexpected sudden death
| Project/Area Number |
17390205
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Jichi Medical University |
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Principal Investigator |
IWAMOTO Sadahiko Jichi Medical University, Dept of Medicine, Professor (10232711)
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| Co-Investigator(Kenkyū-buntansha) |
GOTOH Takaya Jichi Medical University, School of Medicine, Lecturer (80284355)
KUMADA Maki Jichi Medical University, School of Medicine, Assit. Professor (40326830)
OMI Toshinori Nippon Veterinary and Life Science University, 獣医学部, Associate Professor (40296091)
SAKAMOTO Atsushi Jichi Medical University, School of Medicine, Professor (80235168)
KAJII Eiji Jichi Medical University, School of Medicine, Professor (40204391)
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| Project Period (FY) |
2005 – 2007
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| Keywords | genome bank / Hypertension / inflammation / retinol binding protein 4 / association stud / type2 diabetes |
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| Research Abstract |
We have constructed three genome banks. The first genome bank is consisted with almost 1000 Japanese population mainly collected from clinics for hypertension case-control study. The second bank is consisted with 21000 Japanese general population from rural area of all over Japan. The third bank is consisted with almost 1000 Mongolian population.
Using the hypertension case-control genome panel, we found an association of an intronic variable number of tandem repeat polymorphism in an innate immunity associated gene, that is Cold autoinflammatory syndrome 1 (CIAS1, NLRP3). The repeat number correlated with the transcript level in peripheral leukocytes. The high expresser genotype showed higher blood pressure than the low expresser type, and the. CIAS1 expression level correlated with expression of interleukin-1 (3. The transgenic mice expressing human CIAS1 in leukocytes were susceptible to newborn death from severe pneumonitis and aseptic pneumonitis after injection of low dose lipopol
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ysaccharide into adult transgenic mice. The peritoneal -macrophages showed enhanced expression of pre-IL-113 in the cytoplasm and enhanced the extracellular excretion of 1L-1β These data implicated that the expression level of the molecule of innate immunity may be involved in the susceptibility of hypertension through the enhanced inflammatory response.
Insulin resistance is one of the principal pathogenesis of arteriosclerotic disorders. Mongolian diabetic case-control panel was used to survey the association of recently identified adipokine, retinol binding protein. 4 (RBP4). A significant association was shown with a regulatory SNP, minor allele of which enhanced the expression in both hepatocytes and adipocytes. The RBP4 regulatory SNP was also correlated with BMI in Japanese. RBP4 from adipocytes may be involved in the adipogenesis and further insulin resistance.
These population genetics based studies identified several novel loci associated with common diseases. Whether these genetic factors are involved in the forensic cases remains to be assessed. Less
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Research Products
(38 results)
