| Objective:To analyze the distribution of polymorphisms at rs2246012,rs2781659,rs2781666 and rs2781667 of ARG1 gene in Guangxi population,and to compare their differences with populations from different countries,races and regions;To explore the single nucleotide polymorphism of ARG1 gene locus and the genetic susceptibility of bronchial asthma,and further analyze the effect of gene-gene and gene-environment interaction on bronchial asthma.Methods:(1)226 healthy people in Guangxi,who were examined in the Physical Examination Department of the Affiliated Hospital of Youjiang Medical University For Nationalities from September 2020 to March 2022 were collected as the study subjects.Multiple amplification and high-throughput sequencing were used to detect the genotype of ARG1 gene rs2246012,rs2781659,rs2781666 and rs2781667.The results were compared with the SNP data of Han people in southern China,Han people in Beijing,Africans,Americans,Europeans and South Asians published on Ensemble website,and the distribution differences of polymorphisms at selected sites in different regions and ethnic groups were analyzed.(2)A case-control study was used to select 174 patients with asthma diagnosed in the Affiliated Hospital of Youjiang Medical University For Nationalities as the case group,and 226 healthy people in the same period as the control group.Genotypes of the ARG1 gene rs2246012,rs2781659,rs2781666 and rs2781667 were detected by multiple amplification and high-throughput sequencing,and the frequency distribution of genotype and allele was calculated.(3)The indoor environmental factors of the subjects were collected through the questionnaire survey,and the single factor and logistic multiple factor regression analysis was carried out using SPSS24.0 statistical software.(4)The reliability of samples was tested by Hardy-Weinberg’s law of genetic balance.Linkage disequilibrium and haplotype analysis were completed through the SHEsis online tool.(5)The effect of gene-gene and gene-environment interaction on asthma was analyzed by generalized multifactor dimensionality reduction(GMDR).P<0.05 is statistically significant.Results:(1)There was no significant difference in the genotype and allele distribution frequency of the ARG1 gene rs2246012,rs2781659,rs2781666 and rs2781667 loci between the sexes in Guangxi healthy population(P>0.05).(2)The distribution frequency of genotype and allele at rs2246012 locus in Guangxi population was not significantly different from that of Han nationality in Beijing and Han nationality in southern China(P>0.05);Compared with Africans,Europeans and South Asians,the difference was statistically significant(P<0.05);Compared with Americans,the difference in genotype distribution was statistically significant,while the difference in allele distribution was not statistically significant.(3)There was no significant difference in the distribution frequency of rs2781659 genotype and allele between Guangxi population and Americans(P>0.05);Compared with the Han,African,European and South Asian people in Beijing,the difference was statistically significant(P<0.05);Compared with the Han nationality in southern China,there was no statistically significant difference in genotype distribution,but there was statistically significant difference in allele distribution.(4)There was no significant difference in the distribution frequency of rs2781666 genotype and allele between Guangxi population and Americans(P>0.05);Compared with the Han,African,European and South Asian people in Beijing,the difference was statistically significant(P<0.05);Compared with the Han nationality in southern China,the genotype distribution was not statistically significant,but the allele distribution was statistically significant.(5)The distribution frequency of rs2781667 genotype and allele in Guangxi population was significantly different from that in Beijing Han,South China Han,Africans,Europeans and South Asians(P<0.05);Compared with Americans,the difference in genotype distribution was statistically significant,while the difference in allele distribution was not statistically significant.(6)Multivariate logistic regression analysis showed that exposure to hazardous substances in indoor work(P=0.001,OR=16.483)and exposure to fur animals in work and living environment(P=0.001,OR=7.537)were risk factors for asthma;The use of air conditioners(P=0.001,OR=0.248)in the working and living environment and the use of range hoods(P=0.001,OR=0.192)in the family kitchen are protective factors.(7)There was no significant difference in the distribution of rs2246012 genotype and allele between asthma group and control group(P>0.05);The distribution of genotype and allele at rs2781659,rs2781666 and rs2781667 loci in asthma group was significantly different from that in control group(P<0.05).(8)Linkage disequilibrium and haplotype analysis showed that there was strong linkage disequilibrium between the three SNPs rs2781659,rs2781666 and rs2781667;The difference of T-G-T-T haplotypes between the case group and the control group was statistically significant(OR=0.586,95% CI: 0.418-0.820,P=0.00).(9)Analysis of GMDR results showed that there was no significant difference in the interaction between rs2246012,rs2781659,rs2781666,and rs2781667 loci(all P>0.05).In the gene-environment interaction,there was an interaction between indoor work exposure to harmful substances,contact with fur animals,use of air conditioning in work and life,use of kitchen hoods,rs2781659,rs2781666,and rs2781667.Conclusion:(1)There is no difference in the genotype and allele distribution frequency of the ARG1 gene rs2246012,rs2781659,rs2781666 and rs2781667 loci between the sexes in Guangxi healthy population.(2)The distribution of genotypes and alleles at rs2246012,rs2781659,rs2781666 and rs2781667 of ARG1 gene varies in different regions and ethnic groups.(3)The polymorphisms at rs2781659,rs2781666 and rs2781667 of ARG1 gene are related to the susceptibility of adult asthma,while the polymorphisms at rs2246012 are not related to asthma.(4)There is a strong linkage disequilibrium between the three SNPs of ARG1 gene rs2781659,rs2781666 and rs2781667.T-G-T-T haplotype is a protective factor for the occurrence of asthma.(5)The rs2781659,rs2781666,and rs2781667 of the ARG1 gene have synergistic interactions with indoor work exposure to harmful substances,exposure to fur animals,use of air conditioning in work and life,and use of kitchen hoods,which may affect the risk of asthma. |
PDF Full Text Request