母亲MTR基因多态性及其与围孕期叶酸补充的交互作用与子代室间隔缺损的关联研究

阮霄睿; 孙梦婷; 魏剑晖; 罗曼君; 刘涵君; 唐嘉鹏; 李柳萱; 秦家碧

doi:10.7499/j.issn.1008-8830.2403067

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中国当代儿科杂志 ›› 2024, Vol. 26 ›› Issue (9) : 899-906. DOI: 10.7499/j.issn.1008-8830.2403067

论著·临床研究

母亲MTR基因多态性及其与围孕期叶酸补充的交互作用与子代室间隔缺损的关联研究

阮霄睿, 孙梦婷, 魏剑晖, 罗曼君, 刘涵君, 唐嘉鹏, 李柳萱, 秦家碧

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Maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation in relation to offspring ventricular septal defects

RUAN Xiao-Rui, SUN Meng-Ting, WEI Jian-Hui, LUO Man-Jun, LIU Han-Jun, TANG Jia-Peng, LI Liu-Xuan, QIN Jia-Bi

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摘要

目的探讨母亲MTR基因多态性及其与围孕期叶酸补充的交互作用与子代室间隔缺损（ventricular septal defect, VSD）的关联。方法采用病例对照研究，招募426例1岁以内VSD患儿母亲和740例同年龄段健康婴儿母亲。通过问卷调查收集母亲相关暴露信息，并采集其血液标本进行基因多态性检测。采用多因素logistic回归和逆概率加权法处理后logistic回归分析位点与VSD的关联。使用叉生分析和logistic回归分析探讨位点与叶酸补充间的相加和相乘交互作用。结果母亲MTR基因rs6668344位点CT和TT型增加了子代对VSD的易感性（P<0.05）。rs3768139位点GC和CC型、rs1050993位点AG和GG型、rs4659743位点AT和TT型、rs3768142位点GG型、rs3820571位点GT和TT型与VSD发生风险降低有关（P<0.05）。rs6668344位点变异与叶酸补充对VSD存在拮抗相乘交互作用（P<0.05）。结论母亲MTR基因多态性与子代VSD发生显著相关。rs6668344位点变异者围孕期叶酸补充可降低其子代VSD易感性，提示遗传高风险人群更应补充叶酸以预防子代VSD的发生。

Abstract

Objective To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. Methods A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. Results The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). Conclusions Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

导出引用

阮霄睿, 孙梦婷, 魏剑晖, 罗曼君, 刘涵君, 唐嘉鹏, 李柳萱, 秦家碧. 母亲MTR基因多态性及其与围孕期叶酸补充的交互作用与子代室间隔缺损的关联研究[J]. 中国当代儿科杂志. 2024, 26(9): 899-906 https://doi.org/10.7499/j.issn.1008-8830.2403067

RUAN Xiao-Rui, SUN Meng-Ting, WEI Jian-Hui, LUO Man-Jun, LIU Han-Jun, TANG Jia-Peng, LI Liu-Xuan, QIN Jia-Bi. Maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation in relation to offspring ventricular septal defects[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(9): 899-906 https://doi.org/10.7499/j.issn.1008-8830.2403067

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