Study On The Relationship Between Phlegm-heat Syndrome And ACE Gene Polymorphism In Acute Exacerbation Of Chronic Obstructive Pulmonary Disease

Objective The purpose of our study is to study the ancient and modern literature, collate, study of chronic obstructive pulmonary disease etiology and TCM and western medicine. In addition, we also analyze the association between TCM syndrome type and clinical indicators with latest grading for COPD by enrolling the cases and controls. In the last, the study also aimed to analyze the correlation between the polymorphism in the ACE gene and the risk of COPD (syndrome of phlegm-heat obstructing lung).Methods (1) Literature research:Research of ancient and modern literature, a brief overview of syndrome of phlegm-heat obstructing lung for chronic obstructive pulmonary disease in the lung of the history, clinical features, distribution and research progress.(2) Meta-analysis:In order to get precision results of the association between the I/D polymorphism of ACE gene and COPD risk, we performed a meta-analysis to analysis that association based on all published data.(3) Clinical research:A total of194AECOPD patients and194controls were enrolled from the Third People’s Hospital of Chengdu from January2013to January2014. The cases and controls are all matched with sex and age. The AECOPD patients were grouped to Tanre Syndrome and non-Tanre Syndrome according to their clinical symptoms, signs and tongue, pulse. All patients underwent the following tests including routine blood test, erythrocyte sedimentation rate, lung function, blood gas analysis, CRP, PCT and other clinically relevant indicators. COPD draw different syndromes and clinical relevance of indicators based on GOLD2013latest classification.(4) Basic research:Blood samples were collected from the cases and controls. The DNA was extracted; PCR and agarose gel electrophoresis was used to assay ACE genotype. The data for the ACE genotypes and alleles were count, and the association between ACE gene I/D polymorphism and the risk of COPD were analyzed.Results (1) Literature research:The syndrome of phlegm-heat obstructing lung is the major TCM syndrome of AECOPD. The syndrome of phlegm-heat obstructing lung of AECOPD is associated with airway inflammation and airway hypersecretion. The etiology of COPD is associated with many genes.(2) Meta-analysis:A total of11case-control studies were included in the meta-analysis. The results suggested that the I/D polymorphism is associated with the risk of COPD in Asians (DD vs. Ⅱ+DI: OR=2.60,95%CI1.47to4.57, P=0.0009) but not in Europeans (DD vs. Ⅱ+DI: OR=1.01,95%CI0.74to1.39, P=0.93).(3) All the194AECOPD patients,88patients were syndrome of phlegm-heat obstructing lung and106were non syndrome of phlegm-heat obstructing lung according to the TCM classifications. The results of clinical tests indicated that age and the level of CRP were associated with syndrome of phlegm-heat obstructing lung, while the age, BMI, PCT, WBC and other indicators were not associated with syndrome of phlegm-heat obstructing lung.(4) The analyses of the association between the polymorphism of ACE gene and the risk of COPD and COPD with syndrome of phlegm-heat obstructing lung indicated that:the genotype distribution of ACE gene in the COPD group was72,90and28for II, ID and DD genotypes. For the case group, the genotype distributions were82,87and23for Ⅱ, ID and DD genotypes. For the syndrome of phlegm-heat obstructing lung group, the genotype distributions were32.42and11for Ⅱ, ID and DD genotypes. For the Non-syndrome of phlegm-heat obstructing lung group, the genotype distributions were40,48and17for II, ID and DD genotypes. Compared with healthy controls, ACE gene I/D polymorphism does not increase the risk of COPD:OR=1.22,95%CI0.81to1.84; ACE gene I/D polymorphism does not increase the incidence of COPD syndrome of phlegm-heat obstructing lung:OR=1.23,95%CI0.73to2.08; the ACE gene I/D polymorphism does not increase the incidence of COPD risk of non-syndrome of phlegm-heat obstructing lung:OR=1.21,95%CI0.74to1.97. Compared with Non-syndrome of phlegm-heat obstructing lung group, ACE gene I/D polymorphism does not increase the risk of syndrome of phlegm-heat obstructing lung:OR=1.02,95%CI0.70to2.30.Conclusion (1) The I/D polymorphism of ACE gene is associated with the risk of COPD in Asians.(2) Syndrome of phlegm-heat obstructing lung is associated with age and level of CRP;(3) The I/D polymorphism of ACE gene is not associated with Syndrome of phlegm-heat obstructing lung of COPD, and could not be taken as parameter of the classification of TCM syndrome.