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TRAF1/C5和TNF-α基因多态性与结核病易感性分析

吴山客 骆嘉泽 廖寅谦 张开漩 胡宽 邹频昂 汪保国 曾转萍

吴山客, 骆嘉泽, 廖寅谦, 张开漩, 胡宽, 邹频昂, 汪保国, 曾转萍. TRAF1/C5和TNF-α基因多态性与结核病易感性分析[J]. 中华疾病控制杂志, 2024, 28(2): 138-145. doi: 10.16462/j.cnki.zhjbkz.2024.02.003
引用本文: 吴山客, 骆嘉泽, 廖寅谦, 张开漩, 胡宽, 邹频昂, 汪保国, 曾转萍. TRAF1/C5和TNF-α基因多态性与结核病易感性分析[J]. 中华疾病控制杂志, 2024, 28(2): 138-145. doi: 10.16462/j.cnki.zhjbkz.2024.02.003
WU Shanke, LUO Jiaze, LIAO Yinqian, ZHANG Kaixuan, HU Kuan, ZOU Pinang, WANG Baoguo, ZENG Zhuanping. Analysis of TRAF1/C5 and TNF-α gene polymorphisms with susceptibility to tuberculosis[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2024, 28(2): 138-145. doi: 10.16462/j.cnki.zhjbkz.2024.02.003
Citation: WU Shanke, LUO Jiaze, LIAO Yinqian, ZHANG Kaixuan, HU Kuan, ZOU Pinang, WANG Baoguo, ZENG Zhuanping. Analysis of TRAF1/C5 and TNF-α gene polymorphisms with susceptibility to tuberculosis[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2024, 28(2): 138-145. doi: 10.16462/j.cnki.zhjbkz.2024.02.003

TRAF1/C5和TNF-α基因多态性与结核病易感性分析

doi: 10.16462/j.cnki.zhjbkz.2024.02.003
基金项目: 

广东省中医药局项目 20231220

广州市科技计划 202102080272

广州市科技计划 202201010023

广东大学生科技创新培育专项资金 pdjhb0269

详细信息
    通讯作者:

    曾转萍,E-mail: 1141518464@qq.com

  • 中图分类号: R183.3

Analysis of TRAF1/C5 and TNF-α gene polymorphisms with susceptibility to tuberculosis

Funds: 

Project of Traditional Chinese Medicine Bureau of Guangdong Province 20231220

Guangzhou Science and Technology Program Project 202102080272

Guangzhou Science and Technology Program Project 202201010023

Special Fund for Scientific and Technological Innovation Cultivation of College Students in Guangdong pdjhb0269

More Information
  • 摘要:   目的  分析肿瘤坏死因子受体相关蛋白1(tumor necrosis factor receptor-associated factor 1, TRAF1)/补体5(complement component 5, C5) rs10818488和肿瘤坏死因子-α(tumor necrosis factor-alpha, TNF-α) rs1800629基因多态性、环境因素及其交互作用对结核病(tuberculosis, TB)易感性的影响。  方法  选取TB多发家庭中TB确诊患者作为TB病例组,当地社区同期体检的健康志愿者作为健康对照(healthy controls, HC)组,与TB组有血缘关系且共同居住者组成家庭密切接触(healthy household contacts, HHC)组。采用logistic回归分析模型分析基因型和环境因素与TB的关联,叉生分析结合logistic回归分析模型分析基因与环境交互作用。  结果  年龄>45岁(χ2 =7.90, OR=2.28, 95%CI: 1.28~4.04, P=0.005)、吸烟(χ2 =15.27, OR=4.70, 95%CI: 2.16~10.22, P < 0.001)增加HHC组TB发病风险。吸烟(χ2 =13.94, OR=3.58, 95%CI: 1.83~7.01, P < 0.001)、居住地为农村(χ2 =25.05, OR=3.81, 95%CI: 2.26~6.42, P<0.001)和居室环境卫生较差(χ2 =15.31, OR=3.20, 95%CI: 1.79~5.73, P < 0.001)增加HC组TB发病风险。TRAF1/C5 rs10818488位点中,携带AG基因型(共显性及超显性模型)、GG基因型(共显性模型)和AG-GG基因型(显性模型)增加HHC组和HC组患TB风险。TNF-α rs1800629位点与TB易感性暂未显示存在关联。基因与环境交互作用分析显示,在TB组和HHC组间,TRAF1/C5 rs10818488位点AG-GG基因型与吸烟存在协同作用;而在TB组和HC组间,rs10818488位点AG-GG基因型与吸烟和居室环境卫生较差存在协同作用,与居住地存在相乘交互作用,均提高TB发病风险。  结论  TRAF1/C5 rs10818488位点的基因多态性可能与TB发病风险升高有关,且其与吸烟、居住地、居室环境卫生存在交互作用,共同影响TB的易感性。
  • 表  1  TB发病影响因素的单因素分析

    Table  1.   Univariate analysis of influencing factors of TB

    变量  Variables TB组
    group
    HHC组
    group
    HC组
    group
    TB组group∶ HHC组group TB组group∶ HC组group
    χ2
    value
    P
    value
    χ2
    value
    P
    value
    年龄/岁  Age/years 9.85 0.002 0.99 0.318
         < 45 60(45.1) 70(65.4) 88(50.9)
        ≥45 73(54.9) 37(34.6) 85(49.1)
    性别  Gender 14.56 < 0.001 19.91 < 0.001
        男性  Male 91(68.4) 47(43.9) 74(42.8)
        女性  Female 42(31.6) 60(56.1) 99(57.2)
    吸烟  Smoking 32.89 < 0.001 32.10 < 0.001
        否 No 66(49.6) 91(85.0) 139(80.3)
        是 Yes 67(50.4) 16(15.0) 34(19.7)
    饮酒  Alcohol 1.35 0.245 2.48 0.116
        否 No 93(69.9) 82(76.6) 106(61.3)
        是 Yes 40(30.1) 25(23.4) 67(38.7)
    居住地  Residence 0.02 0.902 35.17 < 0.001
        农村  Rural 81(60.9) 66(61.7) 47(27.2)
        城镇  Urban 52(39.1) 41(38.3) 126(72.8)
    居室通风  Ventilation of living room 1.62 0.203 0.01 0.932
        经常  Frequently 115(86.5) 86(80.4) 149(86.1)
        不常  Infrequently 18(13.5) 21(19.6) 24(13.9)
    居室环境卫生  Living room sanitation 1.22 0.269 20.43 < 0.001
        良好  Good 79(59.4) 71(66.4) 143(82.7)
        较差  Poor 54(40.6) 36(33.6) 30(17.3)
    工作环境粉尘暴露  Workplace dust exposure 0.34 0.562 0.30 0.586
        有  Yes 86(64.7) 73(68.2) 117(67.6)
        无  No 47(35.3) 34(31.8) 56(32.4)
    注:TB, 结核病; HHC, 家庭密切接触; HC, 健康对照。
    ①以人数(占比/%)表示。
    Note: TB, tuberculosis; HHC, healthy household contacts; HC, healthy controls.
    ①Number of people(proportion/%).
    下载: 导出CSV

    表  2  TB发病影响因素的多因素分析

    Table  2.   Multivariate analysis of influencing factors of TB

    变量
    Variables
    β值value sx Wald χ2值value OR值value (95% CI) P值value
    TB组group∶HHC组group
      年龄/岁  Age/years
         < 45 1.00
        ≥45 0.82 0.29 7.90 2.28(1.28~4.04) 0.005
      性别  Gender
        女性  Female 1.00
        男性 Male 0.28 0.35 0.61 1.32(0.66~2.62) 0.434
      吸烟 Smoking
        否  No 1.00
        是  Yes 1.55 0.40 15.27 4.70(2.16~10.22) < 0.001
    TB组group∶HC组group
      性别  Gender
        女性  Female 1.00
        男性  Male 0.23 0.32 0.50 1.26(0.67~2.37) 0.482
      吸烟  Smoking
        否  No 1.00
        是  Yes 1.28 0.34 13.94 3.58(1.83~7.01) < 0.001
      居住地  Residence
        城镇  Urban 1.00
        农村  Rural 1.34 0.27 25.05 3.81(2.26~6.42) < 0.001
    TB组group∶HC组group
      居室环境卫生  Living room sanitation
        良好  Good 1.00
        较差 Poor 1.16 0.30 15.31 3.20(1.79~5.73) < 0.001
    注:TB,结核病;HHC,家庭密切接触;HC,健康对照。
    Note: TB, tuberculosis; HHC, healthy household contacts; HC, healthy controls.
    下载: 导出CSV

    表  3  两位点的基因型与等位基因在各组的分布情况

    Table  3.   The genotype and allele distribution of two loci in each group

    位点
    Locus
    基因型/等位基因
    Genotypes/Allele
    TB组
    group
    (n=133)
    HHC组
    group
    (n=107)
    HC组
    group
    (n=173)
    TB组group∶HHC组group TB组group∶HC组group
    χ2
    value
    P
    value
    χ2
    value
    P
    value
    TRAF1/C5 rs10818488 AA 32(24.1) 50(46.7) 82(47.4) 13.60 0.001 19.32 < 0.001
    AG 69(51.9) 40(37.4) 70(40.5)
    GG 32(24.1) 17(15.9) 21(12.1)
    A 133(50.0) 140(65.4) 234(67.6) 11.50 0.001 19.47 < 0.001
    G 133(50.0) 74(34.6) 112(32.4)
    TNF-α rs1800629 AA 2(1.5) 1(0.9) 1(0.6) 1.40 0.496 1.89 0.388
    AG 21(15.8) 23(21.5) 20(11.6)
    GG 110(82.7) 83(77.6) 152(87.8)
    A 25(9.4) 25(11.7) 57(16.5) 0.66 0.416 6.49 0.011
    G 241(90.6) 189(88.3) 289(83.5)
    注:TB, 结核病; HHC, 家庭密切接触; HC, 健康对照。
    ①以人数(占比/%)表示。
    Note: TB, tuberculosis; HHC, healthy household contacts; HC, healthy controls.
    ① Number of people(proportion/%).
    下载: 导出CSV

    表  4  两位点遗传模型与TB的关联性分析

    Table  4.   Association analysis of two locus genetic model and TB

    位点
    Locus
    遗传模型
    Genetic model
    基因型/等位基因
    Genotypes/Allele
    TB组
    group
    (n=133)
    HHC组
    group
    (n=107)
    HC组
    group
    (n=173)
    TB组group∶HHC组group TB组group∶HC组group
    OR值value
    (95% CI)
    P
    value
    OR值value
    (95% CI)
    P值value
    TRAF1/C5 rs10818488 共显性  Co-dominant AA 32(24.1) 50(46.7) 82(47.4) 1.00 1.00
    AG 69(51.8) 40(37.4) 70(40.5) 2.94(1.52~5.66) 0.001 3.17(1.71~5.87) < 0.001
    GG 32(24.1) 17(15.9) 21(12.1) 3.55(1.57~8.03) 0.002 4.50(2.03~9.95) < 0.001
    显性  Dominant AA 32(24.1) 50(46.7) 82(47.4) 1.00 1.00
    AG-GG 101(75.9) 57(53.3) 91(52.6) 3.11(1.69~5.75) < 0.001 3.49(1.95~6.25) < 0.001
    隐性 Recessive AA-AG 101(75.9) 90(84.1) 152(87.9) 1.00 1.00
    GG 32(24.1) 17(15.9) 21(12.1) 1.92(0.94~3.92) 0.073 2.33(1.16~4.65) 0.016
    超显性  Hyper-dominant AA-GG 64(48.1) 67(62.6) 103(59.5) 1.00 1.00
    AG 69(51.9) 40(37.4) 70(40.5) 1.83(1.04~3.24) 0.037 1.89(1.11~3.22) 0.018
    TNF-α rs1800629 共显性 Co-dominant GG 110(82.7) 83(77.6) 152(87.9) 1.00 1.00
    AG 21(15.8) 23(21.5) 20(11.6) 0.74(0.36~1.53) 0.411 1.55(0.69~3.47) 0.286
    AA 2(1.5) 1(0.9) 1(0.5) 0.75(0.06~9.65) 0.822 3.59(0.24~53.87) 0.355
    显性 Dominant GG 110(82.7) 83(77.6) 152(87.9) 1.00 1.00
    AG-AA 23(17.3) 24(22.4) 21(12.1) 0.74(0.36~1.50) 0.400 1.65(0.76~3.59) 0.207
    隐性  Recessive GG-AG 131(98.5) 106(99.1) 172(99.4) 1.00 1.00
    AA 2(1.5) 1(0.9) 1(0.6) 0.79(0.06~10.14) 0.853 3.38(0.23~50.63) 0.377
    超显性  Hyper-dominant GG-AA 112(84.2) 84(78.5) 153(88.4) 1.00 1.00
    AG 21(15.8) 23(21.5) 20(11.6) 0.74(0.36~1.53) 0.417 1.52(0.68~3.40) 0.305
    注:TB, 结核病; HHC, 家庭密切接触; HC, 健康对照。
    ①以人数(占比/%)表示。
    Note: TB, tuberculosis; HHC, healthy household contacts; HC, healthy controls.
    ① Number of people(proportion/%).
    下载: 导出CSV

    表  5  rs10818488位点AG-GG基因型与环境因素相乘交互作用

    Table  5.   Multiplicative interaction of the AG-GG genotype at locus rs10818488 with environmental factors

    组别
    Groups
    交互因素
    Interacting factors
    β
    value
    Wald χ2
    value
    OR值value
    (95% CI)
    P
    value
    TB组group∶HHC组group AG-GG*年龄AG-GG*Age 0.96 2.26 2.61(0.75~9.09) 0.133
    AG-GG*吸烟AG-GG*Smoking 0.21 0.09 1.23(0.32~4.78) 0.762
    TB组group∶HC组group AG-GG*吸烟AG-GG*Smoking 0.15 0.06 1.16(0.35~3.82) 0.807
    AG-GG*居住地AG-GG*Residence 1.83 7.80 6.22(1.72~22.46) 0.005
    AG-GG*居室环境卫生AG-GG*Living room sanitation 1.22 3.44 3.39(0.93~12.31) 0.063
    注:TB,结核病;HHC,家庭密切接触;HC,健康对照。
    Note: TB, tuberculosis; HHC, healthy household contacts; HC, healthy controls.
    下载: 导出CSV

    表  6  叉生分析基因与环境的交互作用

    Table  6.   Crossover analysis of gene-environment interactions

    组别
    Groups
    危险因素
    Risk factors
    基因
    Genes
    环境
    Environment
    病例/对照
    Cases/Controls
    OR值value
    (95% CI)
    P
    value
    RERI值value
    (95% CI)
    S值value
    (95% CI)
    TB组  group∶
    HHC组  group
    TRAF1/C5 rs10818488 *年龄
    TRAF1/C5 rs10818488 *Age
    - - 12/34 1.00 -0.16(-23.62~23.30) 0.98(0.04~27.43)
    + - 48/36 4.90(2.04~11.75) < 0.001
    - + 20/16 4.26(1.53~11.83) 0.005
    + + 53/21 8.00(3.21~19.91) < 0.001
    TRAF1/C5 rs10818488 *吸烟
    TRAF1/C5 rs10818488 *Smoking
    - - 15/41 1.00 12.05(-34.81~58.92) 2.92(0.12~68.93)
    + - 51/50 2.93(1.42~6.04) 0.004
    - + 17/9 5.35(1.93~14.86) 0.001
    + + 50/7 19.34(7.11~52.62) < 0.001
    TB组  group∶
    HC组  group
    TRAF1/C5 rs10818488 *吸烟
    TRAF1/C5 rs10818488 *Smoking
    - - 15/64 1.00 8.77(-27.56~45.10) 2.68(0.11~64.19)
    + - 51/75 3.31(1.61~6.83) 0.001
    - + 17/18 3.90(1.51~10.10) 0.005
    + + 50/16 14.98(6.33~35.47) < 0.001
    TRAF1/C5 rs10818488 *居住地
    TRAF1/C5 rs10818488 *Residence
    - - 6/61 1.00 -0.75(-66.82~65.33) 0.97(0.05~19.93)
    + - 46/65 9.39(3.49~25.21) < 0.001
    - + 26/21 15.01(5.00~45.08) < 0.001
    + + 55/26 22.65(8.13~63.08) < 0.001
    TRAF1/C5 rs10818488 *居室环境卫生
    TRAF1/C5 rs10818488 *Living room sanitation
    - - 21/64 1.00 9.95(-18.69~38.59) 5.91(0.19~183.18)
    + - 58/79 2.49(1.28~4.85) 0.007
    - + 11/18 1.54(0.56~4.24) 0.404
    + + 43/12 12.98(5.33~31.62) < 0.001
    注:TB,结核病;HHC,家庭密切接触;HC,健康对照;RERI,超额相对危险度;S,交互作用指数;TRAF1/C5 rs10818488(+)表示基因型AG-GG,TRAF1/C5 rs10818488(-)表示基因型AA;年龄(+)表示≥45岁,年龄(-)表示 < 45岁;吸烟(+)表示吸烟,吸烟(-)表示不吸烟;居住地(+)表示农村,居住地(-)表示城镇;居室环境卫生(+)表示较差,居室环境卫生(-)表示良好。
    Note: TB, tuberculosis; HHC, healthy household contacts; HC, healthy controls; RERI, relativeexcess risk of interaction; S, the synergyindex; TRAF1/C5 rs10818488 (+) indicates genotype AG-GG and TRAF1/C5 rs10818488 (-) indicates genotype AA; age (+) indicates age greater than or equal to 45 years and age (-) indicates age less than 45 years; smoking (+) indicates smoking and smoking (-) indicates non-smoking; place of residence (+) indicates rural residence and place of residence (-) indicates urban residence; Living room sanitation (+) indicates poor, Living room sanitation (-) indicates good.
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-03-20
  • 修回日期:  2023-08-03
  • 网络出版日期:  2024-03-30
  • 刊出日期:  2024-02-10

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