Association Of CHRNA5-A3 Variation With COPD Risk And Smoking Cessation In Smokers

Objective: COPD is the leading cause of global morbidity and mortality,leading to heavy economic and social burdens.Tobacco use is widely considered to be a major risk factor for COPD.Quit smoking is the only intervention that has evidence to reduce the risk of developing COPD and slow down the decline in lung function in patients with COPD.According to the statistics,the success rate of “do not quit smoking”(does not quit smoking through will and without medication)is less than 3%,and there are many adverse reactions such as epileptic seizures and suicidal tendencies that cause many smokers to deter.Clinically,there is a need for a method to assess the success rate of non-drug quitting to guide accurate smoking cessation.The combination of nicotine and nAChRs is the first step in the rewarding role of nicotine and the basis of nicotine dependence(tobacco dependence).The nicotinic acetylcholine receptor gene(CHRN)regulates the function of nAChRs and plays an important role in the production and persistence of nicotine dependence.Previous studies have found that rs667282 and rs3743073 in CHRNA5-A3 are significantly associated with the occurrence of smoking-related lung cancer.The nicotinic receptor family has a significant association with smoking,smoking cessation,and smoking-induced lung disease.According to the Genome-wide Association Study(GWAS),CHRNA5-A3 encodes nicotinic Acetylcholine Receptors(nAChR)subunits and its Single Nucleotide Polymorphism sites(SNPs)polymorphisms.It plays an important role in the risk of smoking-related lung cancer.To investigate the relationship between the polymorphisms of the two SNPs(CH3A rs3743073 and CHRNA5 rs667282)in the CHRNA5-A3 gene and the smoking susceptibility to COPD and smoking cessation,in order to guide the COPD prevention and smoking cessation by detecting the CHRNA5-A3 polymorphism.Methods: A case-control study was used to collect 180 cases of COPD patients(60 smokers;60 non-drug-assisted smoking cessation patients;60 non-drug-assisted smoking cessation patients)and 60 healthy smokers.The clinical data and peripheral blood specimens were extracted from the blood genomic DNA using a kit(non-centrifuged column method).The CHRNA5-A3 gene fragment was amplified by ordinary PCR.The PCR products were sequenced and the target gene SNP site polymorphism was detected.23.0 Statistical analysis of the association between the SNP polymorphism of the target gene and the susceptibility to COPD and smoking cessation success in smokers.Establish a database,use plink software for Hardy-Weinberg genetic equilibrium analysis,c2 for P value calculation,use Logistic regression model to calculate relative risk relative value(OR)and 95% confidence interval(CI).P<0.05 was considered statistically significant.result:In this study,the genotypes of rs3743073T/G and rs667282T/C loci were analyzed in the control group,which was consistent with Hardy-Weinberg's law of genetic balance,P>0.05.1.There was no statistically significant relationship between the frequency distribution of CHRNA3 rs3743073 and CHRNA5 rs667282 genotypes and the susceptibility to COPD among smoking COPD and smoking healthy people(P>0.05).2.In the study of COPD,CH RNA3 gene locus rs3743073 was associated with smoking cessation success in smoking COPD.Compared with GT mutant heterozygote genotype,GG homozygote carriers had a low success rate of cessation(OR=2.078,95%).CI=1.109-6.615;P=0.027).The CHRNA5 locus rs667282 was associated with the success rate of smoking cessation in COPD patients.Compared with the TC mutant heterozygote genotype,the TT homozygous gene carrier had a low success rate of quitting(OR=2.533,95%CI=1.094-5.866;P=0.028).),more obvious under the over-dominance model,OR=2.413,95% CI=1.159-5.023;P=0.018.There was no statistically significant difference in the success rate of smoking cessation between CHRNA3 rs3743073 and CHRNA5 rs667282 and the severity of COPD.in conclusion: In the study population,the CHRNA5-A3 SNP polymorphism was not associated with the susceptibility and severity of COPD.However,in patients with smoking COPD,the CHRNA5-A3 SNP polymorphism is associated with the success rate of smoking cessation.CHRNA3 rs3743073 GG genotype and CHRNA5 rs667282 TT genotype carriers have low success rates for quitting smoking and need to strengthen smoking cessation therapy.