Genetic Polymorphisms in Sepsis and Cardiovascular Disease: Do Similar Risk Genes Suggest Similar Drug Targets?

Taka-Aki Nakada; Waka Takahashi; Emiri Nakada; Tadanaga Shimada; James A Russell; Keith R Walley

doi:10.1016/j.chest.2019.01.003

Genetic Polymorphisms in Sepsis and Cardiovascular Disease: Do Similar Risk Genes Suggest Similar Drug Targets?

Chest. 2019 Jun;155(6):1260-1271. doi: 10.1016/j.chest.2019.01.003. Epub 2019 Jan 17.

Authors

Taka-Aki Nakada¹, Waka Takahashi², Emiri Nakada³, Tadanaga Shimada⁴, James A Russell⁵, Keith R Walley⁵

Affiliations

¹ Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chuo, Chiba, Japan; Critical Care Research Laboratories, Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada. Electronic address: taka.nakada@nifty.com.
² Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chuo, Chiba, Japan.
³ Critical Care Research Laboratories, Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada; Department of Reproductive Medicine, Chiba University Graduate School of Medicine, Chuo, Chiba, Japan.
⁴ Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chuo, Chiba, Japan; Critical Care Research Laboratories, Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
⁵ Critical Care Research Laboratories, Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.

PMID: 30660782
DOI: 10.1016/j.chest.2019.01.003

Abstract

Genetic variants are associated with altered clinical outcome of patients with sepsis and cardiovascular diseases. Common gene signaling pathways may be involved in the pathophysiology of these diseases. A better understanding of genetic commonality among these diseases may enable the discovery of important genes, signaling pathways, and therapeutic targets for these diseases. We investigated the common genetic factors by a systematic search of the literature. Twenty-four genes (ADRB2, CD14, FGB, FV, HMOX1, IL1B, IL1RN, IL6, IL10, IL17A, IRAK1, MASP2, MBL, MIR608, MIF, NOD2, PCSK9, PPARG, PROC, SERPINE1, SOD2, SVEP1, TF, TIRAP, TLR1) were extracted as reported genetic variations associated with altered outcome of both sepsis and cardiovascular diseases. Of these genes, the adverse allele (or combinations) was same in nine (ADRB2, FV, HMOX1, IL6, MBL, MIF, NOD2, PCSK9, SERPINE1), and the effect appears to be in the same direction in both sepsis and cardiovascular disease. Shared gene signaling pathways suggest that these are true biological results and could point to overlapping drug targets in sepsis and cardiovascular disease.

Keywords: cardiology; critical care; gene polymorphism; septic shock.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cardiovascular Diseases* / drug therapy
Cardiovascular Diseases* / genetics
Critical Care* / methods
Critical Care* / trends
Drug Discovery
Genetic Predisposition to Disease
Humans
Molecular Targeted Therapy / trends
Polymorphism, Single Nucleotide
Sepsis* / drug therapy
Sepsis* / genetics
Signal Transduction* / drug effects
Signal Transduction* / genetics

Grants and funding

FDN 154311/CIHR/Canada