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母亲MTR基因多态性与先天性心脏病易感性关联

李依寰 黄鹏 王婷婷 陈乐陶 张森茂 罗柳 刁静怡 李金琦 孙梦婷 宋欣俐 魏剑晖 刘亦萍 舒靖 秦家碧

李依寰, 黄鹏, 王婷婷, 陈乐陶, 张森茂, 罗柳, 刁静怡, 李金琦, 孙梦婷, 宋欣俐, 魏剑晖, 刘亦萍, 舒靖, 秦家碧. 母亲MTR基因多态性与先天性心脏病易感性关联[J]. 中国公共卫生, 2022, 38(2): 161-166. doi: 10.11847/zgggws1134330
引用本文: 李依寰, 黄鹏, 王婷婷, 陈乐陶, 张森茂, 罗柳, 刁静怡, 李金琦, 孙梦婷, 宋欣俐, 魏剑晖, 刘亦萍, 舒靖, 秦家碧. 母亲MTR基因多态性与先天性心脏病易感性关联[J]. 中国公共卫生, 2022, 38(2): 161-166. doi: 10.11847/zgggws1134330
LI Yi-huan, HUANG Peng, WANG Ting-ting, . Association of maternal MTR gene polymorphism with offspring congenital heart disease: a case-control study[J]. Chinese Journal of Public Health, 2022, 38(2): 161-166. doi: 10.11847/zgggws1134330
Citation: LI Yi-huan, HUANG Peng, WANG Ting-ting, . Association of maternal MTR gene polymorphism with offspring congenital heart disease: a case-control study[J]. Chinese Journal of Public Health, 2022, 38(2): 161-166. doi: 10.11847/zgggws1134330

母亲MTR基因多态性与先天性心脏病易感性关联

doi: 10.11847/zgggws1134330
基金项目: 国家自然科学基金(82073653,81803313);湖南省重点研发计划项目(2018SK2063);湖南省自然科学基金(2018JJ2551);湖南省科技人才托举工程项目(2020TJ – N07);中国博士后科学基金(2020M682644)
详细信息
    作者简介:

    李依寰(1996 – ),女,湖南郴州人,硕士在读,研究方向:围产流行病学

    通信作者:

    秦家碧,E-mail:qinjiabi123@163.com

  • 中图分类号: R 541.1

Association of maternal MTR gene polymorphism with offspring congenital heart disease: a case-control study

  • 摘要:   目的  研究母亲甲硫氨酸合成酶(MTR)基因多态性与子代先天性心脏病(CHD)间的关联性。  方法  于2017年11月 — 2019年12月在湖南省儿童医院心胸外科采用病例对照研究方法,在464例CHD患儿母亲和504例健康儿童母亲中,利用MassArray飞行时间质谱技术对MTR基因的单核苷酸多态性(SNPs)进行检测,采用SPSS24.0和Haploview软件分析MTR基因SNPs及其单倍型与CHD的关联。  结果  rs1266164(TT vs.CC:aOR = 3.39, 95 % CI = 1.48~7.76;隐性模型:aOR = 3.27,95 % CI = 1.44~7.45),rs3768139(CC vs.GG:aOR = 0.26,95 % CI = 0.11~0.58;显性模型:aOR = 0.29,95 % CI = 0.13~0.65;隐性模型:aOR = 0.62,95 % CI = 0.45~0.85),rs1050993(隐性模型:aOR = 0.59,95 % CI = 0.42~0.82),rs6668344(显性模型:aOR = 1.55,95 % CI = 1.12~2.16),rs3820571(GG vs. CC:aOR = 0.28, 95 % CI = 0.12~0.64;隐性模型:aOR = 0.56,95 % CI = 0.40~0.79)等5个位点与子代CHD的发生存在关联。TT和CT单倍型(rs6668344-rs3754255),AGTA单倍型(rs1805087-rs2275565-rs1266164-rs4659743)以及AT和GT单倍型(rs1050993-rs6676866)与CHD的发生相关。  结论  MTR基因多态性与子代CHD的患病存在关联,且其单倍型影响CHD的发生。
  • 表  1  MTR基因位点信息及对照组Hardy-Weinberg平衡检验

    SNPs染色体位置等位基因MAF a分组基因型频率HWE检验
    P
    AA bABBB
    人数%人数%人数%
    rs1266164 Chr1:236887651 C/T 0.1901 对照 344 68.3 150 29.8 10 2.0 0.168
    病例 300 64.7 130 28.0 34 7.3
    rs3768139 Chr1:236864368 C/G 0.2025 对照 10 2.0 150 29.8 344 68.3 0.168
    病例 36 7.8 150 32.3 278 59.9
    rs6676866 Chr1:236901326 G/T 0.4463 对照 104 20.6 244 48.4 156 31.0 0.632
    病例 72 15.5 268 57.8 124 26.7
    rs955516 Chr1:236817204 T/A 0.4143 对照 174 34.5 238 47.2 92 18.3 0.502
    病例 152 32.8 244 52.6 68 14.7
    rs1050993 Chr1:236899005 G/A 0.1643 对照 10 2.0 118 23.4 376 74.6 0.835
    病例 24 5.2 132 28.4 308 66.4
    rs10925252 Chr1:236859062 T/C 0.4318 对照 196 38.9 216 42.9 92 18.3 0.019
    病例 124 26.7 244 52.6 96 20.7
    rs2229276 Chr1:236891269 A/G 0.4525 对照 182 36.1 216 42.9 106 31.7 0.006
    病例 116 25.0 248 53.4 100 21.6
    rs4659743 Chr1:236896087 T/A 0.1767 对照 10 2.0 132 26.2 362 71.8 0.611
    病例 30 6.5 130 28.0 304 65.5
    rs12060570 Chr1:236825769 G/C 0.4101 对照 174 34.5 242 48.0 88 17.5 0.807
    病例 160 34.5 232 50.0 72 15.5
    rs1806505 Chr1:236833275 C/T 0.4123 对照 172 34.1 244 48.4 88 17.5 0.927
    病例 156 33.6 238 51.3 70 15.1
    rs3768142 Chr1:236865264 T/G 0.3905 对照 76 15.1 236 46.8 192 38.1 0.803
    病例 72 15.5 224 48.3 168 36.2
    rs4659724 Chr1:236810824 G/A 0.4256 对照 180 35.7 236 46.8 88 17.5 0.483
    病例 144 31.0 228 49.1 92 19.9
    rs6668344 Chr1:236838026 C/T 0.4215 对照 196 38.9 230 45.6 78 15.5 0.440
    病例 124 26.7 250 53.9 90 19.4
    rs1805087 Chr1:236885200 A/G 0.1064 对照 406 80.6 88 17.5 10 2.0 0.050
    病例 370 79.7 90 19.4 4 0.9
    rs4077829 Chr1:236824490 G/T 0.4163 对照 170 33.7 246 48.8 88 17.5 0.951
    病例 154 33.2 236 50.9 74 15.9
    rs2275565 Chr1:236885376 G/T 0.1643 对照 352 69.8 132 26.2 20 4.0 0.094
    病例 332 71.6 118 25.4 14 3.0
    rs3754255 Chr1:236846557 C/T 0.5021 对照 132 26.2 242 48.0 130 25.8 0.373
    病例 100 21.6 258 55.6 106 22.8
    rs3820571 Chr1:236897133 T/G 0.1736 对照 10 2.0 118 23.4 376 74.6 0.835
    病例 36 7.8 126 27.2 302 65.1
      注:a MAF为最小等位基因频率;b AA = 野生型,AB = 突变纯合子,BB = 突变杂合子。
    下载: 导出CSV

    表  2  病例组和对照组基本情况比较

    基线资料病例组(n = 464)对照组(n = 504)Z/χ2P
    人数%人数%
    怀孕时年龄(岁) 0.191 0.662
     < 35 404 87.1 434 86.1
     ≥ 35 60 12.9 70 13.9
    文化程度 12.306 0.000
     小学或以下 66 14.2 6 1.2
     初中 190 40.9 100 19.8
     高中或中专 130 28.0 168 33.3
     大专或本科及以上 78 16.8 230 45.6
    不良妊娠史(有) 258 55.6 224 44.4 12.033 0.001
    妊娠糖尿病史(有) 44 9.5 18 3.6 14.082 0.000
    妊娠高血压史(有) 30 6.5 10 2.0 12.247 0.000
    家族成员患先天畸形 28 6.0 4 0.8 20.759 0.000
    孕早期感冒 158 34.1 104 20.6 22.030 0.000
    孕早期暴露于二手烟环境 190 40.9 98 19.4 53.451 0.000
    长期居住地附近有可疑污染源 94 20.3 34 6.7 38.443 0.000
    居住地附近有噪声暴露 124 26.7 92 18.3 9.999 0.002
    孕早期服用药物 150 32.3 100 19.8 19.662 0.000
    孕前或孕早期叶酸服用 386 83.2 470 93.3 23.917 0.000
    下载: 导出CSV

    表  3  母亲MTR基因多态性与子代CHD的关联性分析

    SNPs单因素logistic回归多因素logistic回归
    OR95 % CIPaORa95 % CIPFDR-P
    rs1266164
     CC 1 1
     CT 0.99 0.75~1.32 0.965 1.11 0.79~1.55 0.548 0.797
     TT 3.90 1.89~8.03 0.000 3.39 1.48~7.76 0.004 0.043
     显性模型 1.18 0.90~1.54 0.236 1.26 0.92~1.74 0.156 0.416
     隐性模型 3.91 1.91~8.00 0.000 3.27 1.44~7.45 0.005 0.020
    rs3768139
     GG 1 1
     GC 0.28 0.13~0.58 0.001 0.37 0.16~0.85 0.019 0.101
     CC 0.22 0.11~0.46 0.000 0.26 0.11~0.58 0.001 0.032
     显性模型 0.24 0.12~0.49 0.000 0.29 0.13~0.65 0.003 0.048
     隐性模型 0.70 0.53~0.91 0.007 0.62 0.45~0.85 0.003 0.016
    rs1050993
     AA 1 1
     AG 0.47 0.21~1.02 0.055 0.66 0.26~1.64 0.367 0.652
     GG 0.34 0.16~0.73 0.005 0.40 0.17~0.98 0.044 0.201
     显性模型 0.37 0.18~0.79 0.009 0.47 0.19~1.12 0.087 0.278
     隐性模型 0.67 0.51~0.89 0.005 0.59 0.42~0.82 0.002 0.016
    rs6668344
     CC 1 1
     CT 1.72 1.29~2.29 0.000 1.57 1.11~2.23 0.011 0.088
     TT 1.82 1.25~2.66 0.002 1.51 0.96~2.37 0.074 0.237
     显性模型 1.75 1.33~2.29 0.000 1.55 1.12~2.16 0.009 0.048
     隐性模型 1.31 0.94~1.84 0.108 1.14 0.77~1.69 0.517 0.689
    rs3820571
     TT 1 1
     TG 0.30 0.14~0.62 0.001 0.45 0.19~1.06 0.069 0.245
     GG 0.22 0.11~0.46 0.000 0.28 0.12~0.64 0.003 0.048
     显性模型 0.24 0.12~0.49 0.000 0.32 0.14~0.73 0.007 0.056
     隐性模型 0.64 0.48~0.84 0.001 0.56 0.40~0.79 0.001 0.016
      注:a 调整因素为文化程度、不良妊娠史、妊娠糖尿病史、妊娠高血压史、家族成员是否患有先天畸形、孕早期是否感冒、孕早期是否暴露于二手烟环境、长期居住地附近是否有可疑的环境污染源、长期居住地附近是否有公路或者交通干道、孕早期是否服用药物、怀孕前或孕期是否服用叶酸。
    下载: 导出CSV

    表  4  母亲MTR基因单倍型分析结果

    单倍型块单倍型频率(%)病例组对照组χ2POR95 % CI
    计数%计数%
    Block1 TGGC 57.3 529.9 57.1 579.9 57.5 0.036 0.849 1.05 0.88~1.26
    ATCT 39.8 358.0 38.6 412.0 40.9 1.063 0.303 0.95 0.79~1.14
    Block2 CC 48.9 441.1 47.5 505.2 50.1 1.292 0.256 0.93 0.78~1.11
    TT 41.2 413.1 44.5 385.2 38.2 7.921 0.005 1.34 1.11~1.60
    CT 9.0 56.9 6.1 116.8 11.6 17.615 0.000 0.52 0.37~0.72
    Block3 AGCT 64.3 579.8 62.5 664.5 65.9 2.498 0.114 0.89 0.74~1.08
    AGTA 17.0 179.9 19.4 149.9 14.9 6.980 0.008 1.40 1.10~1.78
    GTCT 10.0 89.8 9.7 103.1 10.2 0.164 0.686 0.93 0.69~1.25
    ATCT 5.9 48.1 5.2 66.1 6.6 1.637 0.201 0.82 0.56~1.20
    AGTT 1.7 14.1 1.5 19.4 1.9 0.478 0.489 0.77 0.39~1.54
    Block4 GG 55.1 511.1 55.1 555.4 55.1 0.000 0.992 1.01 0.84~1.21
    GT 28.5 236.9 25.5 314.6 31.2 7.661 0.006 0.77 0.63~0.93
    AT 16.1 175.1 18.9 137.4 13.6 9.796 0.002 1.47 1.15~1.88
      注:Block 1:rs955516-rs4077829-12060570-rs1806505; block 2: rs6668344-rs3754255; block 3: rs1805087-rs2275565-rs1266164-rs4659743; block 4: rs1050993-rs6676866。
    下载: 导出CSV
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  • 接收日期:  2021-02-10
  • 网络出版日期:  2021-12-29
  • 刊出日期:  2022-02-01

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