中国一项前瞻性母婴队列研究：母体一碳代谢基因多态性与不良妊娠结局的关系。
Relationships between Maternal Gene Polymorphisms in One Carbon Metabolism and Adverse Pregnancy Outcomes: A Prospective Mother and Child Cohort Study in China.
机构信息
Key Laboratory of Trace Element Nutrition of National Health Commission, National Institute for Nutrition, Health Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang 050021, China.
出版信息
Nutrients. 2022 May 18;14(10):2108. doi: 10.3390/nu14102108.
Background: To investigate relationships between five single nucleotide polymorphisms (SNP) in four maternal genes involved in one carbon metabolism and adverse pregnancy outcomes, including preterm birth (PTB), low birth weight (LBW), and small-for-gestational-age (SGA). Methods: This was a prospective mother and child cohort study in Wuqiang, China. Pregnant women (n = 939) were recruited from Jun 2016 to Oct 2018. Pregnancy outcomes (PTB, LBW, and SGA) were extracted from medical records and other information including age at childbearing, maternal education level, gravidity, parity, pre-pregnancy weight and height was collected by using a structured questionnaire. The maternal serum folate concentration was measured by using Abbott Architect i2000SR chemiluminescence analyzer in the first prenatal care visit. DNA genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G, and thymidylate synthetase (TYMS) rs3819102 was processed by Sequenom MassARRAY iPLEX Platform. Univariate and multivariate logistics regression analysis were used to test the relationships between 5 SNPs and PTB, LBW, SGA. Results: Totally, 849 dyads of women and infants were included in the analysis. The prevalence of PTD, LBW, and SGA were 3.76%, 1.58%, and 5.31% respectively. The homozygote frequencies of MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G, and TYMS rs3819102 were 44.2%, 1.4%, 6.7%, 1.3%, and 3.2%, and the alt allele frequencies were 66.1%, 10.8%, 24.9%, 10.5%, and 20.5% respectively. The average serum folate concentration was 11.95 ng/mL and the folate deficiency rate was 0.47%. There were no significant associations between MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G, TYMS rs3819102 alleles and PTD, LBW, SGA (p > 0.05). Conclusions: In the population with adequate folate status and low prevalence of adverse pregnancy outcomes, MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G, TYMS rs3819102 alleles may not be related to PTD, LBW, and SGA.
背景
研究了四个参与一碳代谢的母体基因中的五个单核苷酸多态性（SNP）与不良妊娠结局（包括早产、低出生体重和小于胎龄儿）之间的关系。方法：这是在中国武强进行的一项前瞻性母婴队列研究。招募了 939 名孕妇（n=939），招募时间为 2016 年 6 月至 2018 年 10 月。从病历和其他信息中提取妊娠结局（早产、低出生体重和小于胎龄儿），其他信息包括生育年龄、母亲教育水平、孕次、产次、孕前体重和身高，通过使用结构化问卷收集。在第一次产前检查时，使用 Abbott Architect i2000SR 化学发光分析仪测量母血清叶酸浓度。MTHFR C677T 和 A1298C、甲硫氨酸合成酶还原酶（MTRR）A66G、甲硫氨酸合成酶（MTR）A2756G 和胸苷酸合成酶（TYMS）rs3819102 的甲基四氢叶酸还原酶（MTHFR）的 DNA 基因分型通过 Sequenom MassARRAY iPLEX 平台进行。使用单变量和多变量逻辑回归分析来检验 5 个 SNP 与早产、低出生体重、小于胎龄儿之间的关系。结果：共有 849 对母婴纳入分析。早产、低出生体重和小于胎龄儿的患病率分别为 3.76%、1.58%和 5.31%。MTHFR C677T、MTHFR A1298C、MTRR A66G、MTR A2756G 和 TYMS rs3819102 的纯合子频率分别为 44.2%、1.4%、6.7%、1.3%和 3.2%，等位基因频率分别为 66.1%、10.8%、24.9%、10.5%和 20.5%。平均血清叶酸浓度为 11.95ng/ml，叶酸缺乏率为 0.47%。MTHFR C677T、MTHFR A1298C、MTRR A66G、MTR A2756G 和 TYMS rs3819102 等位基因与早产、低出生体重、小于胎龄儿之间无显著相关性（p>0.05）。结论：在叶酸状态充足且不良妊娠结局发生率较低的人群中，MTHFR C677T、MTHFR A1298C、MTRR A66G、MTR A2756G 和 TYMS rs3819102 等位基因可能与早产、低出生体重和小于胎龄儿无关。
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