P. Waltz1, T. Cyr1, R. Namas1, Y. Vodovotz1, R. Shapiro1, B. Zuckerbraun1 1University Of Pittsburgh,Surgery,Pittsburgh, PA, USA
Introduction: HO-1 is an important protein to restore inflammatory and immune homeostasis following stress. Promoter polymorphisms in the HO-1 gene influence the level of HO-1 expression in different organs and tissues to affect response to inflammation and disease. Two specific polymorphisms have been suggested to exert functional importance, including a (GT)n dinucleotide length polymorphism and the T(-413)A single nucleotide polymorphism (SNP). The length polymorphism is better studied with a clear understanding that longer (GT)n repeats exhibits lower HO-1 transcriptional activity. The purpose of these studies was to test the hypothesis that HO-1 polymorphisms associated with higher production of HO-1 protein levels decreases the incidence of nosocomial infection in trauma patients.
Methods: DNA collected prospectively and isolated from 403 trauma patients admitted to the intensive care unit was analyzed retrospectively for both polymorphisms. Demographics, injury severity score, shock index, clinical outcomes including the development of nosocomial infection and multiple organ dysfunciton, as well as cytokines andchemokine analysis was performed.
Results: Polymorphism distribution was similar to that previously described. ~96.5 percent of patients that had a low expressing profile in one polymorphism type, had a high expressing polymorphism in the other type. Nosocomial infection was seen in 22.3% of the population. Individuals that had high expressing HO-1 polymorphisms in both types (AA/GTshort) demonstrated a 0% nosocmial infection rate (0/5 patients) while low expressing polymorphisms in both types (TT/GTlong) hd a 60% nosocmial infection rate (6/10) P<0.05. In patients that presented in shock with higher shock indices, there was a higher rate of nosocmial infeciton. The SNP polymorphisms (AA, AT, TT) were associated with a trend of increasing NI based upon the SNP.
Conclusion: HO-1 polymorphisms associated with higher levels of HO-1 expression were associated with decreased nosomial infections following trauma. Further study is warranted, but these polymorphism may help to understand risk and individualize care moving forward.