The Association Study Between Dopamine D2 Receptor Gene Single Nucleotide Polymorphism And Delirium In Critically Ill Patients

Objective(1)To explore the correlation between dopamine D2(DRD2)receptor gene single nucleotide polymorphism and delirium in critically ill patients.(2)In order to establish a new delirium prediction model,the factor of dopamine D2(DRD2)receptor gene single nucleotide polymorphism was added into the previously established delirium prediction model.The new model improved the early recognition of delirium in critically ill patients.(3)To explore the theoretical foundation of inflammatory theory in delirium.Research MethodsA prospective,single-center,observational study was designed.200 patients admitted to ICU of Lanzhou University Second Hospital from January,2021 to May,2022 were enrolled.Inclusion criteria: age≥18 years old,regardless of gender.The score of prediction model of ICU delirium established was greater than 0.5.Exclusion criteria: delirium on admission;inability to complete an evaluation for delirium;Culling criteria: Length of ICU stay was less than 24 hours;Non-compliant patient.The frequency of genotypes and alleles were measured by single nucleic acid polymorphism technique,and the delirium prediction model of ICU established previously and CAM-ICU assessment scale were used to determine whether delirium occurred and the risk factor of delirium.Analysis:(1)To determine the correlation between dopamine D2 receptor gene single nucleotide polymorphism and delirium in critically ill patients;(2)According to the ICU delirium model established previously,11 factors as follows were collected,including age,history of dementia,history of hypertension,history of coma,APACHEⅡ score,history of delirium,history of emergency surgery,mechanical ventilation,multiple injuries,metabolic acidosis,dexmedetomidine.Combined with the gene frequencies and genotypes of rs6275 and rs6277,this factor was added into the delirium prediction model to establish a new model was constructed by binary Logistics regression.At the same time,the ROC curve was drawn,and the sensitivity and specificity of the model were calculated.(3)According to the identical inclusion and exclusion criteria,the other 100 critically ill patients were collected from May 2022 to November 2022.IL-6,interleukin-8(IL-8)and tumor necrosis factor(TNF-α)were used to explore the mechanism of inflammatory theory in delirium.Research results(1)200 critically ill patients were enrolled in our study,including 127 male(63.5%),with an average age of 57.5±17.95 years old.113 patients received mechanical ventilation(56.5%),among them,28 patients were delirium,and the incidence was 14%.(2)There was no significant difference in rs6275 genotype between the two groups(P=0.068).However,rs6277 genotype was significantly difference between the two groups(P=0.019).In addition,the binary Logistics regression analysis showed that dexmedetomidine(OR=0.330,P=0.026)could effectively prevent delirium in critically ill patients.The(CC)allele of rs6277(OR=2.851,P=0.001)and mechanical ventilation(OR=8.647,95% CI 2.322-32.203,P=0.001)are the risk factor of delirium in critically ill patients.The DRD2 gene polymorphism was added into the new prediction model of delirium in critically ill patients.Its equation=1/[1+exp-(-5.083+0.013×age +0.031×APACHE II score +1.959×mechanical ventilation +0.636×emergency surgery +0.300×history of coma +0.108×multiple injuries +0.508×metabolic acidosis +0.401×history of hypertension +0.491×history of delirium +0.697×history of dementia-1.033×use of dexmedetomide +0.991×DRD2gene polymorphism)],the area under ROC curve of this new model was 0.796.(3)Among the other 100 patients,50% were male and the mean age was56.5±17.15 years old.72 patients received mechanical ventilation,accounting for72%.Delirium was occurred in 13 patients and the incidence of delirium was 13%.The inflammatory factor results showed that there were no significant differences in interleukin-8(P=0.150)and interleukin-6(P=0.171)between the two groups,however,there were significant differences in tumor necrosis factor(TNF-α)(P=0.037).Moreover,the occurrence of delirium is positively correlated with the expression of TNF-α,and its increase may be a predisposing factor for the occurrence of delirium in critically ill patients.Research conclusions(1)Mechanical ventilation and DRD2 gene polymorphism(rs6277 CC genotype)are risk factors of delirium in critically ill patients,however,dexmedetomidine may be the protective factor.(2)While rs6277(CC)genotype was added into the "Lanzhou model",a new delirium prediction model was constructed,and its prediction ability was improved.(3)The increase of TNF-α in peripheral blood was positively correlated with the occurrence of delirium in critically ill patients,and TNF-a > 50.23mmol/L was a risk factor for the occurrence of delirium in critically ill patients.