An Association Study Between Genetic Polymorphisms In The Promoter Of Carbonic Anhydrase â…¢ And Skeletal Muscle Atrophy Of COPD Patients

Objective:To determine the gene sequences of the CAⅢ promoter, To observe the relationship between CA Ⅲ promoter gene polymorphism and skeletal muscle atrophy in the patients with COPD. Discuss whether there is a potential relationship between CA Ⅲ promoter gene polymorphism and susceptibility of skeletal muscle atrophy of COPD Patients.Method:50patients with COPD plus skeletal muscle atrophy,50patients with COPD but have no skeletal muscle atrophy and50healthy volunteers were selected and divided into3groups.2ml of peripheral blood sample was collected each and the DNA of the samples of different groups were extracted. PCR was carried out on the150samples ef for CA Ⅲ gene promoter amplification. The sequencing analysis was made to find the mutation sites in the DNA of CA Ⅲ gene promoter in three groups and all the mutation sites were compaired between different groups to find relationship between CA Ⅲ promoter gene polymorphism and susceptibility of skeletal muscle atrophy of COPD Patients.Results:1.There are eight significant gene mutation sites of the promoter of CA Ⅲ gene sequence, respectively is381(C/A),399(G/A),419(C/T),437(C/G),459(GAT),478(T/C),556(C/G),556(C/G).2. The gene mutation frequencies of the following6gene sites:381th (C/A),399(G/A),419(C/T),478(T/C),556(C/G),556(C/G), were obviously higher than that of control group, with significant difference (P<0.05).But no significant difference was found between the other two groups(P>0.05).3. The frequency of the gene mutation of site437(C/G) in COPD skeletal muscle atrophy group was significantly lower than control group, with significant difference (P<0.05).No difference was showed in the comparison of the control group with the COPD skeletal muscle non-atrophy,COPD skeletal muscle atrophy with COPD skeletal muscle non-atrophy group (P>0.05).4. The frequency of the gene mutation of site459(G/T)in COPD skeletal muscle atrophy group was significantly higher than COPD skeletal muscle non-atrophy group, with significant difference (P<0.05).In the comparison of COPD skeletal muscle trophy group and COPD skeletal muscle non-trophy group with the control group,it had no difference (P>0.05).Conclusion:1.The CA Ⅲ gene promoter polymorphism was possiblely associated with COPD skeletal muscle atrophy.2.1n CA Ⅲ gene promoter polymorphism, gene mutation of the following sites:381th (C/A),399(G/A),419(C/T),459(G/T),478(T/C),556(C/G),556(C/G) increases in COPD skeletal muscle atrophy, which effect possiblely the quantity of CAⅢmRNA and CAⅢ。3.In the CA Ⅲ gene promoter polymorphism, gene mutation sites437th (C/G) decrease in COPD skeletal muscle atrophy, in a sense, is the protective factor.