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NRG1-ErbB4基因多态性与局灶性癫痫易感性的关系

陈新元 吴晖 莫亚雄 韩雁冰 陈新利 朱文叶 黄蕊 唐薇

陈新元, 吴晖, 莫亚雄, 韩雁冰, 陈新利, 朱文叶, 黄蕊, 唐薇. NRG1-ErbB4基因多态性与局灶性癫痫易感性的关系[J]. 昆明医科大学学报, 2021, 42(6): 82-87. doi: 10.12259/j.issn.2095-610X.S20210607
引用本文: 陈新元, 吴晖, 莫亚雄, 韩雁冰, 陈新利, 朱文叶, 黄蕊, 唐薇. NRG1-ErbB4基因多态性与局灶性癫痫易感性的关系[J]. 昆明医科大学学报, 2021, 42(6): 82-87. doi: 10.12259/j.issn.2095-610X.S20210607
Xin-yuan CHEN, Hui WU, Ya-xiong MO, Yan-bing HAN, Xin-li CHEN, Wen-ye ZHU, Rui HUANG, Wen TANG. Association between NRG1-Erbb4 Polymor- phism and Focal Epilepsy[J]. Journal of Kunming Medical University, 2021, 42(6): 82-87. doi: 10.12259/j.issn.2095-610X.S20210607
Citation: Xin-yuan CHEN, Hui WU, Ya-xiong MO, Yan-bing HAN, Xin-li CHEN, Wen-ye ZHU, Rui HUANG, Wen TANG. Association between NRG1-Erbb4 Polymor- phism and Focal Epilepsy[J]. Journal of Kunming Medical University, 2021, 42(6): 82-87. doi: 10.12259/j.issn.2095-610X.S20210607

NRG1-ErbB4基因多态性与局灶性癫痫易感性的关系

doi: 10.12259/j.issn.2095-610X.S20210607
基金项目: 云南省科技计划基金资助项目(2017FE468(-037));云南省科技创新团队基金资助项目(2018HC008);云南省教育厅科学研究基金资助项目(2018JS197)
详细信息
    作者简介:

    陈新元(1994~),男,四川省渠县人,硕士,主要从事药学研究工作

    通讯作者:

    唐薇,E-mail: 964053452@qq.com

  • 中图分类号: R742.1

Association between NRG1-Erbb4 Polymor- phism and Focal Epilepsy

  • 摘要:   目的   研究云南地区患有局灶性癫痫人群的神经调节因子1(Neuregulin-1,NRG1)及其受体ErbB4基因的多态现象与局灶性癫痫易感性的关系。   方法   采用癫痫病例组和健康对照组对比分析,通过Snapshot检测方法,对云南地区的70例局灶性癫痫患者、64例健康对照者进行基因多态现象检测分析,研究对象样本均来自2020年3月到7月昆明医科大学第一附属医院。   结果   发现局灶性癫痫与NRG1(SNP rs35753505, T > C)的多态现象有相关性,NRG1(SNP rs35753505, T > C)基因型( P = 0.007)和等位基因(P = 0.005)的分布差异有统计学意义(P < 0.05)。与此同时,本研究还对NRG1下游受体ErbB4的基因多态性进行分析,发现ErbB4(SNPrs839523,G > A)基因型( P = 0.026)和等位基因(P = 0.013)、(SNPrs707284,A > G)基因型( P = 0.038)和等位基因(P = 0.018)的分布差异有统计学意义(P < 0.05),并且发现SNP rs707284携带的G/G基因型OR值为3.656(95% CI = 1.160-11.525)。   结论   携带突变纯合子G/G基因型的人群患癫痫的易感性较高,NRG1-ErbB4基因多态现象可能共同参与了局灶性癫痫的发生。
  • 表  1  检测基因引物序列(1)

    Table  1.   The primer sequence of tested genes (1)

    单核苷酸多态性 多态性 引物序列 产物长度/bp GC含量
    NRG1 rs35753505 [C/T] 上游引物5′-TTTAAGGCATCAGTTTTCAATAGC-3′
    下游引物5′-TGTCTGGAGAAGGTTTGGAATG-3′
    352 bp 32.1%
    rs6994992 [C/T] 上游引物5′-AGGATTGGATGTTTGAACCACT-3′
    下游引物5′- GGAGGGACAGGGTCATCACA-3′
    202 bp 50.0%
    rs62510682 [G/T] 上游引物5′-GCAAAATCAGCAACATCCTTC-3′
    下游引物5′-TTCCCACGTTATCTCCTACTCTT-3′
    194 bp 37.6%
    ErbB4 rs839523 [A/G] 上游引物5′-CACTTGGAGCATCCTCTTCTG-3′
    下游引物5′-ACTTGGCATGGCATTTGG-3′
    151 bp 38.4%
    rs7598440 [C/T] 上游引物5′-TCACCGCAGGGAATAAAACA-3′
    下游引物5′-CGATGGTAAAAGGCGTGCT-3′
    245 bp 48.2%
    rs707284 [A/G] 上游引物5′-CCACAACTGAGGGTTTTAGGAA-3′
    下游引物5′-TCAGAGGGTGGACGGTGG-3′
    387 bp 38.2%
    下载: 导出CSV

    表  1  检测基因引物序列(2)

    Table  1.   The primer sequence of tested genes (2)

    延伸引物方向 延伸产物 延伸引物长度 延伸引物
    Nrg1 R AG 22 5′-GGAAGCCATGTATCTTTATTTT-3′
    F CT 22 5′-CACCATGCAGGGTTCAAGTGAA-3′
    F GT 48 5′-TTTTTTTTTTTTTTTTTTTTTTTTTTATATGTGTGCAAACAGTTCTTA-3′
    ErbB4 F AG 32 5′-TTTTTTTTTTATTTGCAGATTATTTGCAGCTT-3′
    F CT 32 5′-TTTTTTTTTTGGCTACCCCTGGTAAGAGGGCT-3′
    F AG 42 5′-TTTTTTTTTTTTTTTTTTTTACATGTGCATGGAGTTTTTACC-3′
    下载: 导出CSV

    表  2  NRG1基因多态性与局灶性癫痫易感性关系[n(%)]

    Table  2.   The relationship between NRG1 gene polymorphism and susceptibility to focal epilepsy [n(%)]

    SNP 基因型/等位基因 癫痫组 对照组 Pa OR(95% CI) χ2 Pb
    rs35753505 T/T 13 (18.6) 19 (29.7) 1 9.996 0.007
    C/C 25 (35.7) 8 (12.5) 0.007 0.228 (0.078-0.663)
    C/T 32 (45.7) 37 (57.8) 0.540 0.767 (0.329-1.790)
    T 58 (41.4) 75 (58.6) 1 7.881 0.005
    C 82 (58.6) 53 (41.4) 0.005 0.500 (0.307-0.813)
    rs6994992 C/C 13 (18.6) 14 (21.9) 1 4.445 0.108
    T/C 30 (42.9) 36 (56.3) 0.869 1.078 (0.441-2.638)
    T/T 27 (38.6) 14 (21.9) 0.173 0.500 (0.185-1.354)
    C 56 (40.0) 64 (50.0) 1 2.704 0.100
    T 84 (60.0) 64 (50.0) 0.101 0.667 (0.411-1.082)
    rs62510682 G/G 61 (87.1) 56 (87.5) 1 0.004 0.951
    G/T 9 (12.9) 8 (12.5) 0.951 0.968 (0.349-2.683)
    T/T 0 (0) 0 (0) ----- -----------------
    G 131 (93.6) 120 (93.8) 1 0.004 0.952
    T 9 (6.4) 8(6.3) 0.952 0.970 (0.363-2.596)
      注:a为非条件 logistic 回归分析的P值,b为卡方检验的双侧P值。
    下载: 导出CSV

    表  3  ErbB4基因多态性与局灶性癫痫易感性的关系[n(%)]

    Table  3.   The relationship between the polymorphism of ErbB4 gene and the susceptibility of focal epilepsy [n(%)]

    SNP 基因型/等位基因 癫痫组 对照组 Pa OR(95% CI) χ2 Pb
    rs839523 G/G 15(21.4) 26(40.6) 1 7.333 0.026
    A/A 13(18.6) 5(7.8) 0.015 0.222(0.066~0.745)
    A/G 42(60.0) 33(51.6) 0.047 0.453(0.207~0.991)
    G 72(45.0) 85(66.4) 1 6.182 0.013
    A 68(55.0) 43(33.6) 0.013 0.536(0.327~0.878)
    rs7598440 C/C 18(25.7) 12(18.8) 1 1.129 0.569
    T/C 39(55.7) 37(57.8) 0.420 1.423(0.604~3.356)
    T/T 13(18.6) 15(23.4) 0.302 1.731(0.611~4.905)
    C 75(53.6) 61(47.7) 1 0.936 0.333
    T 65(46.4) 67(52.3) 0.334 1.267(0.784~2.049)
    rs707284 A/A 13(18.6) 6(9.4) 1 6.526 0.038
    A/G 41(58.6) 31(48.4) 0.368 1.638(0.560~4.795)
    G/G 16(22.9) 27(42.2) 0.027 3.656(1.160~11.525)
    A 67(47.9) 43(33.6) 1 5.622 0.018
    G 73(52.1) 85(66.4) 0.018 1.814(1.107~2.975)
      注:a为非条件 logistic 回归分析的P值;b为卡方检验的双侧P值。
    下载: 导出CSV
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