Correlation Analysis Between HO-1 Gene Promoter Polymorphism And Emphysema Severity In Patients With COPD

Objective:In order to provide evidence of chronic obstructive pulmonary disease's(COPD)early diagnosis,condition assessment and individualized treatment.This study analyzes the low attenuation area(LAA)which is detected by CT scan of the chest,and combined with relevant clinical parameters to explore the correlation between the polymorphism of Heme Oxygenase-1(HO-1)promoter(GT)n and the severity of emphysema in patients with COPD.Methods:Based on the 2018 Global Initiative for Chronic Obstructive(GOLD)as the diagnostic criteria,a total of 41 cases of Han nationality COPD patients from Southwest China were included,who were admitted to the second department of Respiratory and critical care medicine of the First Affiliated Hospital of Kunming Medical University from April 2019 to December 2019.Once recruited,the relevant clinical parameters of the inpatient(including age,gender,smoking index,main symptoms,body mass index(BMI),dyspnea score(mMRC score),annual acute exacerbations,the durations of COPD),the laboratory indicators(including serum bilirubin,white blood count(WBC),neutrophil percentage,eosinophil percentage,hemoglobin amount),and the auxiliary examination(including forced expiratory volume in the first second?Forced Expiratory Volume in 1 second(FEV1)/Forced Vital Capacity(FVC),the actual value of forced expiratory volume in the first second as a percentage of the expected value(FEV1%)were collected.At the same time,all the subjects were tested by CT scan to calculate the low attenuation area(LAA),which is the indicator of emphysema severity.Collected the fasting venous blood samples from all subjects,then sequenced and analysised the(GT)n promoter polymorphism of the HO-1 gene in the patients.According to the number of redundant fragments(GT)n in the HO-1 promoter gene of the patients with COPD,it can be Divided into the three types as following:S group(GT)n<27 repeats,M group 27 repeats?(GT)n?32 repeats,and L group(GT)n>32 repeats;The types of subjects' alleles were divided into L+group(with L allele:L/L,L/M,L/S)and L-group(without L allele:M/M,M/S,S/S);Statistical analysis of the above-mentioned related clinical parameters and LAA%of the two groups of patients with different(GT)n polymorphisms.Results:In the study,a total of 41 inpatients with COPD were included.They were grouped according to whether carried with the HO-1 promoter L-type allele,the 17 subjects in the L+group and the 24 subjects in the L-group.The results showed that LAA%of the two groups of subjects was significant different(?2=-2.329,P=0.020),suggesting that the subjects in the L+group showed more severe emphysema than the L-subjects.In the lung function test,the two groups of subjects had significant differences between FEV1%and FEV1/FVC(P>0.05)(Z=-2.978,P=0.003;t=-3.078,P=0.004),it is suggested that the airflow limitation of the subjects in group L+is more obvious than that in group L-.From the perspective of clinical symptoms,the differences between the two groups of subjects with shortness of breath were statistically significant(?2=4.797,P=0.026),and the proportion of subjects with shortness of breath in the L+group was higher than the L-group;there were no significant differences in the others' symptoms(P>0.05).In terms of clinical comorbidities,all of the 17 subjects in the L+group,10 had respiratory failure,8 had pulmonary artery hypertension,8 had chronic pulmonary heart disease,2 had hypertension,and 4 had pulmonary infections;Of all the 24 L-group subjects,7 were with respiratory failure,11 were with pulmonary hypertension,5 were with pulmonary heart disease,2 were with hypertension,and 5 were with pulmonary infection;the results showed that the complications of respiratory failure were differently between the two groups(?2=6.388,P=0.011).The proportion of subjects with respiratory failure in the L+group was higher;the differences between other complications were not statistically significant(P>0.05).And in the durations of COPD between the groups,there was statistically significant(Z=-2.016,P=0.044),It suggested that the disease duration of the participants in the L-group was longer.The comparison of patients in GOLD grade 1?4 of groups was difference(?2=10.567,P=0.014),and there were no significant differences in the BMI,smoking index,the duration of disease,the number of annual exacerbations,and the mMRC score(P>0.05).From the laboratory indicators,the level of serum bilirubin between the groups was difference significantly(t=-2.439,P=0.019),The L-group's was higher than that in the L+group;there was no significant difference between their WBC,hemoglobin,eosinophil percentage,and neutrophil percentage(P>0.05).Furthermore,there was no correlation between the GOLD grades of COPD and the LAA%,serum bilirubin level,BMI in the subjects(P>0.05).Conclusion:1.L-group subjects showed higher levels of serum bilirubin and a longer durations of disease,it may suggesting that bilirubin levels were negatively correlated with patient's disease progression.L+group subjects' disease progression may be faster than L-group,it could be related to the expression of HO-1 was being inhibited or the enzyme activity had being decreased in patients in the L+group.2.COPD subjects who carrying L-type alleles have shortness of breath as the main clinical manifestation and are more likely complicate with respiratory failure;and the lung function examination of L+group subjects shows more obvious airflow limitation,and in The distribution ratio of GOLD 3?4 is higher.3.The HO-1 promoter(GT)n gene polymorphism is related to the severity of emphysema in COPD subjects;COPD subjects carrying with L-type alleles show more LAA%and more severe emphysema under chest CT.The HO-1 promoter(GT)n sequence that does not carry the L-type allele may help protect the lung from reactive oxygen exposure and prevent the development of emphysema.