Genetic polymorphisms in severe sepsis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24689066
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Chiba University
• Principal Investigator: TAKAAKI Nakada 千葉大学, 医学(系)研究科(研究院), 特任講師 (20375794)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 敗血症 / 遺伝子多型

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.

Free Research Field

救急医学