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中华妇幼临床医学杂志(电子版) ›› 2021, Vol. 17 ›› Issue (02) : 198 -206. doi: 10.3877/cma.j.issn.1673-5250.2021.02.011

所属专题： 文献；

论著

MTHFR基因C677T多态性与儿童孤独症谱系障碍发病风险的Meta分析
王思思, 伍金林†()   
  • 收稿日期:2020-07-08 修回日期:2021-02-27 出版日期:2021-04-01
  • 通信作者: 伍金林

Association between MTHFR gene C677T polymorphism and risk of autism spectrum disorder in children: a Meta-analysis

Sisi Wang, Jinlin Wu†()   

  • Received:2020-07-08 Revised:2021-02-27 Published:2021-04-01
  • Corresponding author: Jinlin Wu
  • Supported by:
    Applied Basic Research Project of Science and Technology Department of Sichuan Province(2021YJ0211); Popularization Application Project of Health Commission of Sichuan Province(20PJ070)
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引用本文：

王思思, 伍金林. MTHFR基因C677T多态性与儿童孤独症谱系障碍发病风险的Meta分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2021, 17(02): 198-206.

Sisi Wang, Jinlin Wu. Association between MTHFR gene C677T polymorphism and risk of autism spectrum disorder in children: a Meta-analysis[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(02): 198-206.

目的

探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与儿童孤独症谱系障碍(ASD)发病风险的相关性。

方法

计算机检索PubMed、EMbase、Cochrane Library、维普中文科技期刊数据库、中国知网(CNKI)和万方数据知识服务平台，搜集有关MTHFR基因C677T多态性与ASD发病风险的病例对照研究(CCS)，检索时限均从建库至2019年6月。由2位研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用Stata 14.0软件进行Meta分析。

结果

按照本研究设定的文献检索策略，14篇文献纳入本研究，共计纳入患儿4 141例，其中研究组为确诊为孤独症谱系障碍的患儿，共2 024例，对照组为未患遗传性或神经性疾病儿童，共2 117例。本研究Meta分析结果显示：①MTHFR基因C677T多态性等位基因模型(T vs C)与ASD发病风险有关(OR＝1.99，95%CI：1.41～2.79，P<0.001)，按研究对象的人群进行进一步分析，结果显示，MTHFR基因C677T多态性等位基因模型(T vs C)在高加索人群与ASD发病风险相关(OR＝1.66，95%CI：1.19～2.30，P<0.001)，在亚洲人群与ASD发病风险无关(OR＝2.31，95%CI: 0.93～5.75，P<0.001)。②在纯合子模型(TT vs CC)及杂合子模型(CT vs CC)模型下，MTHFR基因C677T多态性均与ASD发病风险有关(OR＝1.65，95%CI：1.12～2.42，P＝0.011；OR＝1.60, 95%CI：1.26～2.02，P<0.001)。

结论

高加索地区人群MTHFR基因C677T多态性与ASD发病风险有相关性，但是在亚洲人群中，MTHFR基因C677T多态性与ASD发病风险无关。

关键词: 亚甲基四氢叶酸还原酶, 孤独性障碍, 人种群, 等位基因, Meta分析, 病例对照研究, 儿童
Objective

To study to evaluate the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and the risk of autism spectrum disorder (ASD) in children.

Methods

PubMed, EMbase, Cochrane Library, VIP, China National Knowledge Infrastructure (CNKI) and Wanfang databases were electronically searched to collect case-control (CCS) studies about the association between the MTHFR gene C677T polymorphism and the risk of ASD in children from inception to June 2019. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. The Meta-analysis was performed using Stata 14.0 software.

Results

According to the literature retrieval strategies of this study, 14 pieces of CCS literature (4 141 cases) were included in final Meta-analysis, including 2 024 cases diagnosed with ASD in study group and 2 117 cases with out any genetic or neurological disorders in control group.The results of Meta-analysis showed as the following. ① The MTHFR gene C677T polymorphism allele model (T vs C) was associated with risk of ASD in children (OR=1.99, 95%CI: 1.41-2.79, P<0.001). Further analysis was carried out according to the population of study subjects. The results showed that the MTHFR gene C677T polymorphism allele model (T vs C) was associated with risk of ASD in children in Caucasian (OR=1.66, 95%CI: 1.19-2.30, P<0.001), was not associated with risk of ASD in children in Asian (OR=2.31, 95%CI: 0.93-5.75, P<0.001). ②In the homozygous model (TT vs CC) and heterozygous model (CT vs CC), MTHFR gene C677T polymorphism was associated with risk of ASD in children (OR=1.65, 95%CI: 1.12-2.42, P=0.011; OR=1.60, 95%CI: 1.26-2.02, P<0.001 ).

Conclusions

MTHFR gene C677T polymorphism is associated with risk of ASD in children in Caucasian. However, in Asian, MTHFR gene C677T polymorphism is not associated with risk of ASD in children.

Key words: Methylenetetrahydrofolate reductase (NADPH2), Autistic disorder, Ethnic groups, Alleles, Meta analysis, Case-control studies, Child
图1 文献筛选流程及结果
表1 14篇有关MTHFR基因C677T多态性与ASD发病风险的CCS文献的基本特征
文献(第1作者，文献发表年) 患儿例数 地区 患儿年龄(岁，±s) 男、女性患儿性别比
研究组 对照组 研究组 对照组 研究组 对照组
El-Baz, 2017[11] 31 39 高加索地区 4.57±2.00 — — —
Guo[12], 2012 186 186 亚洲地区 — — — —
Ismail[13], 2019 78 80 其他地区 4.6 — 65∶13 —
Liu[14], 2011 205 384 高加索地区 —   — 1∶1
Mohammad[15], 2009 138 138 亚洲地区 4.4±1.7 4.4±1.6 20∶3 20∶3
James[18], 2006 356 205 高加索地区 7.3±3.2 10.8±4.1 — —
Pasca[19], 2009 39 80 高加索地区 6.90±0.82 8.3±0.8 31∶8 29∶26
Santos[20], 2010 151 100 高加索地区 — — 116∶35 57∶43
Schmidt[21], 2011 294 180 高加索地区 — — — —
Shawky[22], 2014 20 20 高加索地区 4.57±1.36 4.9±1.6 13∶7 13∶7
Meguid[23], 2015 24 30 高加索地区 — — — —
Park[24], 2014 251 425 亚洲地区 — — 107∶11 253∶170
Zhang[25], 2018 201 200 亚洲地区 — — — —
Divyakolu[26], 2013 50 50 其他地区 — — — —
表2 14篇有关MTHFR基因C677T多态性与ASD发病风险的CCS文献纳入患儿的基因型分布
文献(第1作者，文献发表年) 研究组基因型 对照组基因型 Hardy-Weinberg平衡检验
CC CT TT CC CT TT χ2值 P值
El-Baz[11], 2017 12 15 4 35 4 0 0.114 0.736
Guo[12], 2012 79 77 30 87 83 16 0.371 0.542
Ismail[13], 2019 37 28 13 60 17 3 1.497 0.221
Liu[14], 2011 68 98 39 177 166 41 0.050 0.823
Mohammad[15], 2009 98 35 5 120 18 0 0.935 0.412
James[18], 2006 134 176 46 93 90 22 0.001 0.974
Pasca[19], 2009 21 14 4 46 28 6 0.356 0.551
Santos[20], 2010 60 68 23 45 41 14 0.862 0.353
Schmidt[21], 2011 128 133 33 74 77 29 1.375 0.241
Shawky[22], 2014 7 10 3 14 6 0 0.623 0.429
Meguid[23], 2015 11 11 2 20 8 2 0.833 0.361
Park[24], 2014 76 136 37 139 204 80 0.113 0.737
Zhang[25], 2018 32 101 68 42 86 71 2.721 0.099
Divyakolu[26], 2013 27 22 1 42 8 0 0.378 0.538
表3 纳入研究14篇有关MTHFR基因C677T多态性与ASD发病风险的CCS文献的偏倚风险评价(分)
文献(第一作者，文献发表年份) 对象选择 可比性 暴露水平 总分
El-Baz[11]，2017 1 2 3 6
Guo[12]，2012 3 1 2 6
Ismail[13]，2019 2 1 2 5
Liu[14]，2011 2 1 2 5
Mohammad[15]，2009 3 2 3 8
James[18]，2006 3 1 3 7
Pasca[19]，2009 2 1 3 6
Santos[20]，2010 3 1 3 7
Schmidt[21]，2011 4 1 3 8
Shawky[22]，2014 2 2 2 6
Meguid[23]，2015 3 2 3 8
Park[24]，2014 3 1 2 6
Zhang[25]，2018 4 1 3 8
Divyakolu[26]，2013 2 1 2 5
图2 MTHFR基因C677T多态性等位基因模型(T vs C)与ASD发病风险的Meta分析结果
图3 MTHFR基因C677T多态性纯合子模型(TT vs CC)与ASD发病风险的Meta分析结果
图4 MTHFR基因C677T多态性杂合子模型(CT vs CC)与ASD发病风险的Meta分析结果
图5 剔除单个研究后进行敏感性分析等位基因模型(T vs C)
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