Study On The Differences Of TCM Constitutions,the Balance Of Th17/Treg And ADAM33Gene Polymorphism Between "Fast" And"Slow" Development Of Chronic Obstructive Pulmonary Disease Patients

Objective:The paper attempts to discuss the impact of Taditional Chinese Medcine constitution, Th17/Treg and related cytokine imbalance as well as ADAM33gene single nucleotide polymorphisms (SNPs) on the "fast" and "slow" development of COPD patients, so as to provide the research basis for COPD prediction and prevention strategies. Method:1) Cross-sectional observation study on255outpatient and inpatient cases of stable COPD patients from February2012to June2013has been conducted by No.4Affiliated Hospital of Xinjiang Medical University. The unified questionnaire and TCM constitution scale have been filled by all of the patients for TCM constitution assessment with the analysis of susceptible constitutional type of COPD patients in Urumqi, Xinjiang. Through the comparison of constitution distribution characteristics for the "fast" development group and "slow" group, the pathology constitution which might affect the rapid development of sickness can be analyzed;2) Epidemiological survey in communities at the same phase as well as the healthy people in the MEC of No.4Affiliated Hospital of Xinjiang Medical University can be taken as the control group. The intracellular colored flow cytometry can be used to detect the Th17/Treg cell proportion in the peripheral blood of the cases groups and control groups; The Cytometric Beads Array detection can be applied to relevant cytokines such as IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17A; ELISA is used to detect TGF-(3level in the serum of subjects, so as to discuss the impact of Th17/Treg as well as relevant cytokines imbalance on COPD Patients of different development speed;3) Through meta analysis of literatures published before June30th,2013about ADAM33gene T1, S1, S2, F+1polymorphism and COPD susceptibility to evaluated the relationship between ADAM33gene polymorphisms and COPD susceptibility. Results:1) In general, COPD patients shows the distinct constitution distribution characteristics, yang vacuity constitution, qi vacuity constitution, and qi depression constitution in the stable phase, which account for29.01%,33.33%, and15.29%among all the COPD patients in the stable phase respectively. qi vacuity constitution, phlegmatic hygrosis constitution, and qi depression constitution in "fast" development group were higer than "slow" group, The P is0.000,0.000and0.003respectively.Differences of distribution proportion of yang vacuity constitution and qi vacuity constitution in "fast" group and "slight" group,the P is0.011,0.006respectively. The individual constitution distribution difference is unified by dividing the patients into≥level Ⅲ lung function and≤level Ⅱ, the results of which show that there is statistical difference in the two groups of phlegmatic hygrosis constitution (Χ2=5.920, P=0.015), yin deficiency constitution (Χ2=5.775, P=0.016) and qi vacuity constitution (Χ2=7.700, P=0.006).2) The Thl7/Treg and TNF-a level for stable COPD patients in "fast" development group is significantly higher than other cases groups and control groups(P <0.01); Th17/Treg and IL-6level for COPD patients of level "D" after the classification division in accordance with the level of danger is relatively higher than that of other groups with the existence of statistical difference (P<0.01). IL-4is clearly higher in the peripheral blood of normal smoking group than in the other three groups (P=0.027), and it is positively correlated with the smoking index (r=0.097P=0.0313) and IL-17A (r=0.275P=0.028).3) It is assessed by the system with Meta analysis that T1variant genotypes (A/G, G/G) of ADAM33gene can increase the risk of COPD for people in China (OR=2.07,95%CI=1.09-3.95), while the T1variant genotype of people in Caucasian has not increased COPD risk. whose OR is0.95(95%CI=0.65-1.39). S1locus variant genotypes (C/T+T/T) of ADAM33gene for Chinese groups has increased the risk of COPD significantly (OR=1.46,95%CI=1.15-1.84), while the variant genotype of Caucasian groups hasn’t increased the risk of COPD (OR=0.52,95%CI=0.15-1.85).4) S2locus variant genotypes (C/T+T/T) of ADAM33gene for Chinese Han population in Xinjiang has decreased the risk of COPD greatly (OR=0.402,95%CI=0.158-1.021). There is no distinct difference for the distribution of T1, S1, S2, F+1locus mutation genotype of ADAM33gene for the "fast" development group,"slow" group,"slight" group and "serious" group. Conclusions:1) Yang deficiency constitution, vital energy deficiency constitution, vital energy depression constitution are susceptible ones for COPD, and the vital energy depression constitution is correlated with the progress of COPD.2) There is the Th17/Treg immune imbalance state for peripheral blood of stable COPD patients in the phase, which is related to the damage degree of lung function of patients as well as the sicknes development speed; The high expression of TNF-a and IL-6in the peripheral blood of COPD patients may be dangerous factors relevant to the sickness; IL-4may be a protective cytokine related to COPD.3) Meta analysis shows that the significant T1and S1locus mutation of ADAM33gene can increase the risk of COPD for Chinese groups significantly. Besides, there may be racial or regional different for COPD susceptibility by ADAM33gene polymorphism. But we found in this study S2locus mutation of ADAM33gene could decrease the risk of COPD for Han population in Xinjiang, there is no association of T1, S2, F+1, F1mutation of ADAM33gene with susceptibility to "fast" development of COPD, this association may exist in others genes or other regions of ADAM33need to be further demonstrated.