| Budget Amount *help |
¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
Fiscal Year 2014: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Outline of Final Research Achievements |
Mortality from septic shock is highly heritable. The identification of causal genetic factors is insufficient. To discover key contributors, we first identified non-synonymous single nucleotide polymorphisms (SNPs) in conserved genomic regions that are predicted to have significant effects on protein function. We then test the hypothesis that these non-synonymous SNPs across the genome alter clinical outcome of septic shock. Septic shock patients (n=520) were genotyped for the 843 non-synonymous SNPs. Patients with septic shock having the SVEP1 C allele of non-synonymous SNP, SVEP1 rs10817033 had a significant increase in the hazard of death over the 28-day and increased organ dysfunction, and needed more organ support (P<0.05). Silencing SVEP1 significantly increased IL-8, GRO-alpha, MCP-1 and MCP-3 production in HUVECs under LPS stimulation (P<0.01). C allele of SVEP1 SNP was associated with increased 28-day mortality and organ dysfunction of septic shock.
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