| Objectives To explore the association between the six positive sites in the genome-wide association study of IL-33 gene rs2381416,rs928413,and IL1RL1 gene rs3771180,rs13408661,rs1420101,rs10197862 and the incidence of asthma in Guangxi Zhuang population,and further study the genetic mechanism of asthma in Guangxi Zhuang population.Methods A case-control study was conducted on 113 patients with asthma and 104 healthy subjects.Collect the genomic DNA from the peripheral blood of the research subjects,and then select the rs2381416,rs928413,rs3771180,rs13408661,rs1420101,and rs10197862 in the IL-33 and IL1RL1 genes through the GWAS Catalog database.Subsequently,the primers of the above six sites were designed in combination with SNP database.SNP sites were genotyped by multiple LDR-PCR,and then the products were sequenced to identify the genotype of each site.SPSS 22.0 and SHEsis software were used to analyze the essential characteristics of the research object,Hardy-Weinberg equilibrium test,differences in genotype distribution,differences in an allele frequency distribution,and the association between different genetic models at each site and asthma.Haploview 4.2 was used to analyze linkage disequilibrium between loci and further construct haplotypes to investigate the correlation between each haplotype and asthma.Results 1.Statistical results of essential characteristics:There was no statistically significant difference in gender,average age,and BMI between the case group and the control group(P>0.05).2.Correlation analysis results of each gene locus:(1)The frequency distribution of genotypes and alleles in the case group and control group conformed to Hardy-Weinberg equilibrium(P>0.05).(2)There were polymorphisms in six loci of IL-33 gene rs2381416,rs928413,and IL1RL1 gene rs3771180,rs13408661,rs1420101,rs10197862 in Guangxi Zhuang population.(3)The distribution of genotype and allele frequency of these 6 loci between the two groups was not statistically significant.(4)The correlation between the different genetic models of six loci(allele model,homozygous model,heterozygous model,dominant model,recessive model)and asthma showed no statistical significance.3.The results of linkage disequilibrium and haplotype analysis among the six loci:there is linkage disequilibrium(D`>0.8)and"strong LD"(r~2>0.33)between rs2381416 and rs928413 located in IL-33 gene.There is a linkage disequilibrium between the four positions of rs3771180,rs13408661,rs1420101,and rs10197862 located in the IL1RL1 gene(D`>0.8),and there is a"strong LD"between rs3771180 and rs13408661,rs10197862,and rs13408661 and rs10197862(r~2>0.33).Haploview 4.2 was used to construct haplotypes between the sites with linkage disequilibrium:rs2381416 and rs928413 constitute haplotype block 1,and rs3771180,rs13408661,rs1420101,and rs10197862 constitute haplotype block2.The distribution of haplotypes AA,AG,CG of haplotype block 1 between the case group and the control group showed no significant difference(P>0.05),the distribution of haplotypes GGCA,GGTA,TACG,TATG haplotypes in haplotype block 2 between the case group and the control group was not statistically significant(P>0.05).Conclusion(1)There were polymorphisms in two loci of IL-33 gene rs2381416 and rs928413 in Guangxi Zhuang asthmatic population.(2)There were polymorphisms in four loci of IL1RL1 gene rs3771180,rs13408661,rs1420101,rs10197862 in Guangxi Zhuang asthmatic population.(3)The genotype,allele frequency,and genetic model distribution of these six loci were not different between Guangxi Zhuang people with asthma and healthy people.(4)The haplotype of AA,AG,and GG composed of rs2381416 and rs928413and the haplotype of GGCA,GGTA,TACG,and TATG composed of rs3771180,rs13408661,rs1420101,and rs10197862 may not be related to the incidence of asthma in Guangxi Zhuang population. |
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