Association Of Nrf2,hmox1 Gene Polymorphism With Chronic Obstructive Pulmonary Disease In Chinese Mongolian Population In Inner Mongolia

[Objectives]Chronic obstructive pulmonary disease(COPD)is a common chronic respiratory disease with high incidence in middle-aged and elderly people.It is characterized by persistent airflow limitation and exposure to dangerous factors such as cigarette smoke and other harmful particles or gases.The chronic inflammatory response is related.There are many researches on the pathogenesis of COPD,and recent studies have shown that the mechanism of oxidative stress is an important mechanism.Nuclear factor E2 related factor 2(NRF2)is a key factor in cellular oxidative stress response.When the reactive oxygen species(ROS)is produced too much,NRF2 can be activated,and the activated NRF2 can be transferred into the nucleus to induce the increase of the expression of the antioxidant gene heme oxygenase 1(HMOX1),which plays an important role in the oxidation-antioxidant balance of COPD.The previous GWAS study of the COPD family found that the NRF2 gene rs6706649 and rs6721961 loci and the HMOX1 gene rs2071747 locus were associated with COPD.In this study,a large sample of sporadic population was used to verify the relationship between NRF2 gene rs6706649 and rs6721961 loci,HMOX1 gene rs2071747 polymorphism and genetic susceptibility of Mongolian COPD in Inner Mongolia,so as to identify genes that play an important role in the development of COPD.Target site.[Methods](1)This study included 1144 Mongolian samples from 12 Qicheng County hospitals in Inner Mongolia,including 650 COPD patients and 494 healthy controls.Collect 5 ml of venous blood and perform lung function test;(2)Genomic DNA was extracted by DNA extraction kit from QIAGEN,Germany,and the concentration and purity of DNA were determined by Nanodrop 2000 micro spectrophotometer.The OD value was between 1.8 and 2.0,and the DNA concentration was at least 50 ng/ul.Not less than 500ug;(3)NRF2,HMOX1 gene rs6706649,rs6721961,rs2071747 were classified into 1144 samples by SNPscan high-throughput genotyping technique,and the typing data were analyzed by SPSS software.[Results](1)The distribution of rs6706649,rs6721961,and rs2071747 in the Mongolian population of Inner Mongolia in this study accorded with the Hardy-Weinberg equilibrium;(2)By analyzing the allele frequency and genotype frequency,the frequency of C allele frequency of rs6706649 in NRF2 gene was 94.7%and 90.8%in the control group and COPD group,respectively,and the difference was statistically significant(P<0.05);In the control group,the CC genotype frequency was 89.9%,the CT genotype frequency was 9.72%,and the TT genotype frequency was 0.38%.In the COPD group,the CC genotype frequency was 83.4%,the CT genotype frequency was 14.8%,and the TT gene.The frequency of type was 1.8%,and the genotype frequency(CC,CT,TT)was statistically significant(P<0.05);the allele frequency and genotype frequency of NRF2 gene rs6721961 locus,HMOX1 gene rs2071747 locus There was no significant difference between the COPD group and the control group(P>0.05).(3)Through genetic model analysis,under the codominant genetic model,individuals carrying C/T genotypes relative to C/C genotypes can increase the risk of chronic obstructive pulmonary disease(OR=1.632,95%CI:0.129-2.360),P=0.009),individuals carrying T/T genotypes relative to C/C genotypes can also increase the risk of chronic obstructive pulmonary disease(OR=4.081,95%CI:0.890-18.721,P=0.022);Under the genetic model,the C/TT/T genotype relative to the C/C genotype was also a risk factor for COPD(OR=1.769,95%CI:1.237-2.531,P=0.003);under the recessive genetic model,The T/T genotype was also a risk factor for chronic obstructive pulmonary disease compared with the C/CC/T genotype(OR=4.627,95%Cl:1.031-20.796,P=0.023);under the overdominant genetic model,C/T Genotypes relative to C/CT/T genotypes significantly increased the risk of COPD(OR=1.610,95%CI:1.114-2.327,P=0.01);NRF2 gene rs6721961 locus,HMOX1 gene rs2071747 locus in various There was no statistical difference between the COPD group and the control group in the genetic model analysis(P>0.05)[Conclusion](1)The NRF2 gene rs6706649 is associated with the risk of COPD in Mongolian population in Inner Mongolia,and the C>T mutation increases the risk of COPD.The T allele of rs6706649 is a risk factor for Mongolian COPD in Inner Mongolia.;(2)NRF2 gene rs6721961 locus,HMOX1 gene rs2071747 locus had no significant relationship with the genetic susceptibility of Mongolian COPD in Inner Mongolia.