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Genetic Makeup Influences Susceptibility to Severe Sepsis

Chicago — (June 11, 2010) 

In the June Anesthesiology researchers take aim at identifying genetic risk factors for sepsis – a leading cause of death for critically ill patients.

Genetic makeup has been identified as a key factor leading to the development of sepsis, a systemic inflammatory reaction that occurs during infection. Sepsis is considered severe when associated with organ dysfunction.

Connections Between Genetic Composition and Disease Risk
In humans, multiple copies of some genes can occur and these multiple copies vary greatly among individuals. Large scale copy number variations (CNVs) were recently identified throughout the entire human genome. CNVs affect gene expression and patient response characteristics by altering the number of copies of a gene present in a cell or nucleus. This affect on gene dosage can cause disease or present risk to the development of complex traits.

“CNVs constitute a major source of inter-individual genetic variation and might represent a major factor in the cause of complex traits such as response to infection and sepsis,” said XiangMing Fang, M.D., of the Department of Anesthesiology, the First Affiliated Hospital, School of Medicine at Zhejian University in Hangzhou, China. “It is believed that detection of both CNVs and conventional genetic marker single nucleotide polymorphisms (SNPs) will provide deep insight into the genetic and immune mechanism underlying sepsis.”

Background Information
Another consideration for genetic risk of sepsis involves one group of white blood cells, Neutrophils. They are the body’s first line of defense against infection, migrating to an infection site to engulf and kill microbes. Due to neutrophil activation during sepsis, the levels of neutrophil peptides 1-3 are greatly increased in the blood of patients with the disease. These peptides play an important role in infectious and inflammatory diseases.

The genes encoding human neutrophil peptides 1-3, (DEFA1/DEFA3) exhibit CNVs. Dr. Fang and colleagues set out to determine whether DEFA1/DEFA3 CNVs was related to patient susceptibility to infection induced by complications such as severe sepsis.

Study Results and Conclusions
The team found that the genotype DEFA1/DEFA3 with >8 copies was more frequent in patients with severe sepsis than in the control group (55.9 percent vs. 31.3 percent). The established association between the genotype and severe sepsis was replicated in the second age and gender matched case controlled cohort.

Researchers concluded that DEFA1/DEFA3 is an important genetic component participating in the immune response to severe sepsis as a higher copy number of DEFA1/DEFA3 (>8 copies) is significantly associated with risk of severe sepsis.

“This study is the first to demonstrate that CNVs, within DEFA1/DEFA3 contribute significantly to susceptibility to severe sepsis,” said Dr. Fang. “This finding may help to identify patients at high risk for predisposition to severe sepsis so that preventative interventions and personalized therapy can be implemented.”

For more information, visit the Anesthesiology website at


Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific society with more than 52,000 members organized to raise and maintain the standards of the medical practice of anesthesiology. ASA is committed to ensuring physician anesthesiologists evaluate and supervise the medical care of patients before, during and after surgery to provide the highest quality and safest care every patient deserves.

For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at . To learn more about the role physician anesthesiologists play in ensuring patient safety, visit Like ASA on Facebook , follow ASALifeline on Twitter and follow ASA on LinkedIn .



American Society of Anesthesiologists