Genetic makeup has been identified as a main factor leading to the development of sepsis, an inflammatory reaction that affects the whole body (systemic) that occurs during infection. When associated with organ dysfunction, sepsis is considered severe.
In the June issue of medical journal Anesthesiology scientists take aim at identifying genetic risk factors for sepsis – a leading cause of death for critically ill patients.
Connections Between Genetic Composition and Disease Risk
In human beings, multiple copies of some specific 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 changing the number of copies of a gene present in a cell or nucleus. This effect on gene dosage can cause disease or present risk to the development of complex traits.
XiangMing Fang, M.D., of the Department of Anesthesiology, the First Affiliated Hospital, School of Medicine at Zhejian University in Hangzhou, China, said:
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. 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.
Another consideration for sepsis genetic risk involves Neutrophils – a group of blood cells; the body’s first line of defense against infection, which migrate to an infection site to engulf and destroy 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 (copy number variations). Dr. Fang and team set out to find out whether DEFA1/DEFA3 CNVs was associated with patient susceptibility to infection triggered by complications, such as severe sepsis.
The researchers 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 linked to severe sepsis risk.
Dr. Fang said:
This study is the first to demonstrate that CNVs, within DEFA1/DEFA3 contribute significantly to susceptibility to severe sepsis. 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.
Increased Genomic Copy Number of DEFA1/DEFA3 Is Associated with Susceptibility to Severe Sepsis in Chinese Han Population
Chen, QiXing; Hakimi, Matthew; Wu, ShuiJing; Jin, Yue; Cheng, BaoLi; Wang, HaiHong; Xie, GuoHao; Ganz, Tomas; Linzmeier, Rose M.; Fang, XiangMing
Anesthesiology. 112(6):1428-1434, June 2010.
Written by Christian Nordqvist