Prediction Of Hospital Acquired Infection Based On The Genomic Copy Number Polymorphism Of DEFA1/DEFA3 In Critical Ill Patients

Background:Human neutrophil peptides(HNP)1-3,subfamilies of a-defensins,compose the frontlineofinnateimmuneandadaptiveimmunedefenseagainstpathogens.DEFA1/DEFA3,the genes encoding HNP 1-3,display wide-ranging copy number polymorphism(CNP)and are associated with infection in critical ill patients.Hospital acquired infection(HAI)is related to many genetic factors,and DEFA1/DEFA3 CNP may result in the individual difference of hereditary susceptibility of hospital acquired infection.Methods:HAI Patients and control patients in Intensive care unit(ICU)are enrolled from August 1,2013 to November 30,2016 randomly.The CNP of DEFA1/DEFA3 was determined by real-time quantitative polymerase chain reaction(RT q-PCR)after extracting DNA from peripheral whole blood samples.Also other clinical characteristics such age,sex,diagnosis,Acute Physiology Score(APS),Acute Physiology and Chronic Health Evaluation score II(APACHE II)score,Sequential Organ Failure Assessment score(SOFA)score,culture of pathogen and outcomes were obtained.Statistical analysis was performed by SPSS 20.0 software.Results:One hundred and six critical ill patients with hospital acquired infection were enrolled in HAI group while 109 in control group with no significant difference in age and sex.Copy numbers of DEFA1/DEFA3 ranged from 2 to 16 per diploid genome in all 215 critical ill patients with a median of 7 copies.In HAI group,the copy numbers of DEFA1/DEFA3 varied from 2 to 12 copies and the median number was six.While in patients with no HAI,the CNP of DEFA1/DEFA3 was significant higher(ranged from 2 to 16 with median of eight,p =0.017).Fifty two point eight percentage of HAI patients had got less than seven copies compared with a frequency of only 35.8%in control group(p=0.014,OR,0.497,95%CI,0.288-0.859).Combining the DEFA1/DEFA3 CNP with clinical characteristics,the comprehensive model which predicts the incidence of HAI showed a better predictive ability with area under the receiver operating characteristic(AUROC)of 0.759(95%CI 0.694-0.823).Conclusions:DEFA1/DEFA3 is an important genetic component participating in host immune response to HAI.A higher DEFA1/DEFA3 copy number(CNP>7),will contribute to the lower susceptibility to HAI in critical ill patients.Combining the DEFA1/DEFA3 CNP with clinical characteristics,the comprehensive model which predicts the incidence of HAI showed a better predictive ability.