Relationship between TBX21 gene polymorphism and susceptibility to asthma in Han children
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摘要:
目的 探讨汉族儿童T-box转录因子21(TBX21) 基因多态性，并分析其与哮喘易感性的相关性。 方法 选取2019年1月—2021年1月河南省儿童医院收治的汉族哮喘患者190例，设为哮喘组，另选取同期本院健康体检的汉族儿童135名作为对照组。采集口腔黏膜标本，分析rs9910408、rs16947078、rs2240017基因位点单核苷酸多态性(SNP)，比较2组3个基因位点基因型分布及等位基因频率，采用logistic回归分析研究TBX21 基因rs2240017位点多态性与哮喘易感性的关系。 结果 Hardy-Weinberg平衡检验结果显示，rs9910408、rs16947078、rs2240017基因型在2组儿童中的分布频率未发生偏移，研究对象代表性良好。哮喘组与对照组rs2240017基因型等级分布，差异有统计学意义(P < 0.05)，且哮喘组C等位基因频率显著高于对照组(89.47% vs. 40.37%，P < 0.05)，G等位基因频率显著低于对照组(10.53% vs. 59.63%，P < 0.05)。2组rs9910408、rs16947078基因型等级分布，差异无统计学意义(均P＞0.05)。经logistic回归分析，TBX21 基因rs2240017的G/G、C/G、C/C基因型及G等位基因频率降低、C等位基因频率升高可能是哮喘易感性的影响因素(P < 0.05)。 结论 TBX21 基因rs2240017位点多态性与哮喘易感性密切相关。 -
关键词:
- 哮喘 /
- T-box转录因子21 /
- 儿童 /
- 基因位点单核苷酸多态性 /
- 易感性
Abstract:Objective To explore the polymorphism of T-box transcription factor 21 (TBX21) in children of Han nationality and analyze its association with asthma susceptibility. Methods A total of 190 Han asthma patients admitted to the paediatrics department of Henan Children' s Hospital from January 2019 to January 2021 were selected as the asthma group, and 135 Han children who underwent physical examination in our hospital during the same period were selected as the control group. Oral mucosa specimens were collected; single nucleotide polymorphisms (SNP) were analysed at rs9910408, rs16947078 and rs2240017 gene loci, and the genotype distribution and allele frequencies of the 3 loci, including the TBX21 gene, were compared between the two groups. The relationship between rs2240017 locus polymorphism and asthma susceptibility was analysed by logistic regression. Results The Hardy-Weinberg balance test showed that the distribution frequencies of rs9910408, rs16947078 and rs2240017 genotypes in the two groups of children did not shift, and the research subjects were well represented. The difference in rs2240017 genotype distribution between the asthma group and control group was statistically significant (P < 0.05), and the frequency of the C allele in the asthma group was significantly higher than that of the control group (89.47% vs. 40.37%, P < 0.05). Moreover, the frequency of the G allele was significantly lower than that of the control group (10.53% vs. 59.63%, P < 0.05). No statistically significant difference in the rs9910408 and rs16947078 genotypes distribution was observed between the two groups (P>0.05). Logistic regression analysis showed that the decrease of G/G, C/G, C/C genotypes and G allele frequencies, as well as the increase of C allele frequency of TBX21 gene rs2240017 may be the influencing factor of asthma susceptibility (P < 0.05). Conclusion The rs2240017 polymorphism of the TBX21 gene is closely related to asthma susceptibility. -
表 1 TBX21 基因SNPs位点基因信息
Table 1. Gene information for TBX21 gene SNPs locus
SNPs 定位 等位基因 基因频率 rs9910408 5'near gene G/A 0.095 rs16947078 exon_1 G/A 0.121 rs2240017 exon_1 C/G 0.136 
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表 2 TBX21 基因SNP位点引物序列
Table 2. Primer sequence for TBX21 gene SNPs locus
基因位点 上游引物(5′-3′) 下游引物(5′-3′) rs9910408 ACGTTGGATGAGAACGCCATGTCGCTTCC ACGTTGGATGTTCTTGCCCCCACTCCCAG rs16947078 ACGTTGGATGTCATATCTAATGAAGGGAGC ACGTTGGATGTCTTGGAGGAACTGTGGTTG rs2240017 GGGTTGCGGAGACATGCTG ACTCACCGTCCCTGCTTG
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表 3 2组儿童一般资料比较
Table 3. Comparison of general data between the two groups of children
组别 例数 年龄(x±s，岁) 性别[例(%)] 身高(x±s，m) 体重(x±s，kg) 烟雾暴露史[例(%)] 男 女 哮喘组 190 8.36±3.51 103(54.21) 87(45.79) 1.48±0.15 28.56±10.25 76(40.00) 对照组 135 8.31±3.47 72(53.33) 63(46.67) 1.47±0.13 28.02±9.38 42(31.11) 统计量 0.127a 0.024b 0.625a 0.485a 2.697b P值 0.899 0.876 0.532 0.628 0.101 注：a为t值，b为χ2值。
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表 4 基因位点Hardy-Weinberg遗传平衡检验
Table 4. Hardy - Weinberg genetic balance test for gene loci
基因位点 χ2值 P值 哮喘组 对照组 哮喘组 对照组 rs9910408 1.581 2.523 0.256 0.147 rs16947078 3.816 0.167 0.692 0.733 rs2240017 2.394 0.122 0.136 0.798
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表 5 2组儿童rs9910408位点基因型及等位基因频率分布[例(%)]
Table 5. Genotype and allele frequency distribution of the rs9910408 locus in 2 groups of children[cases (%)]
组别 例数 基因型 等位基因 G/G G/A A/A G A 哮喘组 190 56(29.47) 63(33.16) 71(37.37) 175(46.05) 205(53.95) 对照组 135 39(28.89) 45(33.33) 51(37.78) 123(45.56) 147(54.44) χ2值 0.013 0.016 P值 0.993 0.900
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表 6 2组儿童rs16947078位点基因型及等位基因频率分布[例(%)]
Table 6. Genotype and allele frequency distribution of the rs16947078 locus in 2 groups of children[cases (%)]
组别 例数 基因型 等位基因 A/A A/G G/G G A 哮喘组 190 24(12.63) 65(34.21) 101(53.16) 267(70.26) 113(29.74) 对照组 135 13(9.63) 46(34.07) 76(56.30) 198(73.33) 72(26.67) χ2值 0.768 0.005 P值 0.005 0.942
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表 7 2组儿童rs2240017位点基因型及等位基因频率分布[例(%)]
Table 7. Genotype and allele frequency distribution of the rs2240017 locus in 2 groups of children[cases (%)]
组别 例数 基因型 等位基因 G/G C/G C/C G C 哮喘组 190 4(2.11) 32(16.84) 154(81.05) 40(10.53) 340(89.47) 对照组 135 76(56.30) 9(6.67) 50(37.03) 161(59.63) 109(40.37) χ2值 124.994 178.172 P值 ＜0.001 ＜0.001
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表 8 变量赋值情况
Table 8. Variable assignment
变量 赋值方法 哮喘易感性 否=0，是=1 基因型 C/G=0，G/G或C/C=1 等位基因频率 G频率降低且C频率升高=0，G频率升高且C频率降低=1
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表 9 TBX21 基因rs2240017多态性与哮喘易感性关系
Table 9. Relationship between rs2240017 polymorphism of TBX21 gene and asthma susceptibility
变量 B SE Wald χ2 P值 OR值 95% CI 基因型 G/G 0.963 0.521 3.416 0.031 2.260 1.326~3.194 C/G 1.264 0.421 9.014 0.027 3.540 2.347~4.733 C/C 1.027 0.613 2.807 0.012 2.793 1.527~4.059 等位基因频率 G频率降低 1.759 0.871 3.163 0.006 4.707 2.781~6.633 C频率升高 1.475 0.896 2.710 ＜0.001 4.371 3.024~5.817
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