The inflammatory response is influenced by FXIII VAL 34 LEU polymorphism in a human LPS model.
BACKGROUND
In sepsis, activation of coagulation and inhibition of fibrinolysis lead to microvascular thrombosis. The Val34Leu polymorphism affects the function of FXIII by increasing the rate of FXIII activation by thrombin, which results in an increased and faster rate of fibrin stabilization. Sepsis and multi-organ failure cause disturbance of the normal balance of inflammation and coagulation, one of the most frequent causes of death in ICU patients. Research in polymorphism has shown the possible influence of FXIII in coagulation and inflammation.


METHODS
We analyzed the influence of the common FXIII Val34Leu polymorphism on inflammatory and coagulation parameters in human experimental endotoxinemia. Healthy volunteers (n = 62) received 2 ng endotoxin (LPS) per kg body weight as a bolus infusion over 2 min. We developed a new mutagenic separated PCR assay for determination of the FXIII promoter polymorphism.


RESULTS
FXIII levels were higher for homozygous carriers of the FXIII polymorphism in comparison with wild-type 34 Val/Val and heterozygous 34 Val/Leu. Interestingly, persons homozygous for the FXIII Val34Leu polymorphism had lower monocyte and neutrophil counts throughout the observation period, yet prothrombin fragment 1+2 and D-dimer levels did not differ after LPS challenge.


CONCLUSIONS
Our findings indicate that the common FXIII Val34Leu polymorphism is associated with differences in monocyte and neutrophil cell counts in response to systemic LPS infusion in humans.
Kovar
Florian M
FM
Department of Trauma Surgery, Medical University of Vienna, Vienna, Austria.
Marsik
Claudia L
CL
Jilma
Bernd
B
Mannhalter
Christine
C
Joukhadar
Christian
C
Wagner
Oswald F
OF
Endler
Georg
G
D000293:Adolescent; D000328:Adult; D005176:Factor XIII / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D008070:Lipopolysaccharides; D009000:Monocytes / Q000276:immunology*; D018375:Neutrophil Activation / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
D008070:Lipopolysaccharides; C064015:factor XIII subunit A; D005176:Factor XIII