母亲<italic>MTR</italic>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

doi:10.7499/j.issn.1008-8830.2403067

摘要
图/表
参考文献(30)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (640 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

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。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	阮霄睿
	孙梦婷
	魏剑晖
	罗曼君
	刘涵君
	唐嘉鹏
	李柳萱
	秦家碧

关键词 ：室间隔缺损, MTR基因, 单核苷酸多态性, 逆概率处理加权, 交互作用, 子代

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.

Key words： Ventricular septal defect MTR gene Single nucleotide polymorphism Inverse probability of treatment weighting Interaction Offspring

收稿日期: 2024-03-19

基金资助:国家自然科学基金项目（82073653、81803313）；湖南省杰出青年基金项目（2022JJ10087）。

通讯作者: 秦家碧，男，教授。Email：qinjiabi123@163.com。 E-mail: qinjiabi123@163.com

作者简介: 阮霄睿，女，博士研究生；

引用本文:

阮霄睿,孙梦婷,魏剑晖等. 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.

RUAN Xiao-Rui,SUN Meng-Ting,WEI Jian-Hui et al. Maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation in relation to offspring ventricular septal defects[J]. CJCP, 2024, 26(9): 899-906.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2403067 或 http://www.zgddek.com/CN/Y2024/V26/I9/899

	Triedman JK, Newburger JW. Trends in congenital heart disease: the next decade[J]. Circulation, 2016, 133(25): 2716-2733. PMID: 27324366. DOI: 10.1161/CIRCULATIONAHA.116.023544.
	GBD 2017 Congenital Heart Disease Collaborators. Global, regional, and national burden of congenital heart disease, 1990-2017: a systematic analysis for the global burden of disease study 2017[J]. Lancet Child Adolesc Health, 2020, 4(3): 185-200. PMID: 31978374. PMCID: PMC7645774. DOI: 10.1016/S2352-4642(19)30402-X.
	Lopez L, Houyel L, Colan SD, et al. Classification of ventricular septal defects for the Eleventh Iteration of the International Classification of Diseases—striving for consensus: a report from the International Society for Nomenclature of Paediatric and Congenital Heart Disease[J]. Ann Thorac Surg, 2018, 106(5): 1578-1589. PMID: 30031844. DOI: 10.1016/j.athoracsur.2018.06.020.
	Zhao L, Chen L, Yang T, et al. Birth prevalence of congenital heart disease in China, 1980-2019: a systematic review and meta-analysis of 617 studies[J]. Eur J Epidemiol, 2020, 35(7): 631-642. PMID: 32519018. PMCID: PMC7387380. DOI: 10.1007/s10654-020-00653-0.
	He Q, Dou Z, Su Z, et al. Inpatient costs of congenital heart surgery in China: results from the National Centre for Cardiovascular Diseases[J]. Lancet Reg Health West Pac, 2023, 31: 100623. PMID: 36879787. PMCID: PMC9985056. DOI: 10.1016/j.lanwpc.2022.100623.
	Li X, Li S, Mu D, et al. The association between periconceptional folic acid supplementation and congenital heart defects: a case-control study in China[J]. Prev Med (Baltim), 2013, 56(6): 385-389. PMID: 23480969. DOI: 10.1016/j.ypmed.2013.02.019.
	Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal mulitivitamin use[J]. Am J Epidemiol, 2000, 151(9): 878-884. PMID: 10791560. DOI: 10.1093/oxfordjournals.aje.a010291.
	Leirgul E, Gildestad T, Nilsen RM, et al. Periconceptional folic acid supplementation and infant risk of congenital heart defects in Norway 1999-2009[J]. Paediatr Perinat Epidemiol, 2015, 29(5): 391-400. PMID: 26212116. DOI: 10.1111/ppe.12212.
	Bedard T, Lowry RB, Sibbald B, et al. Folic acid fortification and the birth prevalence of congenital heart defect cases in Alberta, Canada[J]. Birth Defects Res A Clin Mol Teratol, 2013, 97(8): 564-570. PMID: 23913528. DOI: 10.1002/bdra.23162.
	Bailey LB, Gregory JF. Folate metabolism and requirements[J]. J Nutr, 1999, 129(4): 779-782. PMID: 10203550. DOI: 10.1093/jn/129.4.779.
	卢艳, 王海琴, 王新. 高同型半胱氨酸血症孕鼠与其仔鼠发生先天性心脏病的关系[J]. 中南大学学报（医学版）, 2011, 36(1): 68-73. PMID: 21311142. DOI: 10.3969/j.issn.1672-7347.2011.01.011.
	Rosenquist TH, Ratashak SA, Selhub J. Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid[J]. Proc Natl Acad Sci U S A, 1996, 93(26): 15227-15232. PMID: 8986792. PMCID: PMC26385. DOI: 10.1073/pnas.93.26.15227.
	Xu X, Ye B, Li M, et al. The UA doppler index, plasma HCY, and Cys C in pregnancies complicated by congenital heart disease of the fetus[J]. J Clin Med, 2022, 11(19): 5962. PMID: 36233829. PMCID: PMC9573527. DOI: 10.3390/jcm11195962.
	14 宫婷, 李芬, HuangH, 等. MTR、MTRR基因多态性与先天性心脏病的相关性研究[J]. 第三军医大学学报, 2010, 32(2): 127-130. DOI: 10.16016/j.1000-5404.2010.02.022.
	Raina JK, Panjaliya RK, Dogra V, et al. "Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case-control study encompassing meta-analysis and trial sequential analysis"[J]. BMC Pediatr, 2022, 22(1): 223. PMID: 35468734. PMCID: PMC9036697. DOI: 10.1186/s12887-022-03227-z.
	Li WX, Dai SX, Zheng JJ, et al. Homocysteine metabolism gene polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) jointly elevate the risk of folate deficiency[J]. Nutrients, 2015, 7(8): 6670-6687. PMID: 26266420. PMCID: PMC4555142. DOI: 10.3390/nu7085303.
	Liu Y, Zhong T, Song X, et al. Association of MTR gene polymorphisms with the occurrence of non-syndromic congenital heart disease: a case-control study[J]. Sci Rep, 2023, 13(1): 9424. PMID: 37296303. PMCID: PMC10256807. DOI: 10.1038/s41598-023-36330-x.
	Liu W, Wang J, Chen LJ. Association between MTR A2756G polymorphism and susceptibility to congenital heart disease: a meta-analysis[J]. PLoS One, 2022, 17(7): e0270828. PMID: 35802641. PMCID: PMC9269412. DOI: 10.1371/journal.pone.0270828.
	Deng C, Deng Y, Xie L, et al. Genetic polymorphisms in MTR are associated with non-syndromic congenital heart disease from a family-based case-control study in the Chinese population[J]. Sci Rep, 2019, 9(1): 5065. PMID: 30911047. PMCID: PMC6433945. DOI: 10.1038/s41598-019-41641-z.
	Zhao JY, Qiao B, Duan WY, et al. Genetic variants reducing MTR gene expression increase the risk of congenital heart disease in Han Chinese populations[J]. Eur Heart J, 2014, 35(11): 733-742. PMID: 23798577. DOI: 10.1093/eurheartj/eht221.
	21 涂博祥, 秦婴逸, 吴骋, 等. 倾向性评分加权方法介绍及R软件实现[J]. 中国循证医学杂志, 2022, 22(3): 365-372. DOI: 10.7507/1672-2531.202111101.
	Harmon DL, Shields DC, Woodside JV, et al. Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations[J]. Genet Epidemiol, 1999, 17(4): 298-309. PMID: 10520212. DOI: 10.1002/(SICI)1098-2272(199911)17:4<298::AID-GEPI5>3.0.CO;2-V.
	Su J, Li Z. Analysis of MTR and MTRR gene polymorphisms in Chinese patients with ventricular septal defect[J]. Appl Immunohistochem Mol Morphol, 2018, 26(10): 769-774. PMID: 29293099. PMCID: PMC6250295. DOI: 10.1097/PAI.0000000000000512.
	24 李依寰, 黄鹏, 王婷婷, 等. 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.
	Shaw GM, Lu W, Zhu H, et al. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects[J]. BMC Med Genet, 2009, 10: 49. PMID: 19493349. PMCID: PMC2700092. DOI: 10.1186/1471-2350-10-49.
	Swanson DA, Liu ML, Baker PJ, et al. Targeted disruption of the methionine synthase gene in mice[J]. Mol Cell Biol, 2001, 21(4): 1058-1065. PMID: 11158293. PMCID: PMC99560. DOI: 10.1128/MCB.21.4.1058-1065.2001.
	Menezo Y, Elder K, Clement A, et al. Folic acid, folinic acid, 5 methyl tetrahydrofolate supplementation for mutations that affect epigenesis through the folate and one-carbon cycles[J]. Biomolecules, 2022, 12(2): 197. PMID: 35204698. PMCID: PMC8961567. DOI: 10.3390/biom12020197.
	28 刘虹, 李勇, 叶鸿瑁, 等. 同型半胱氨酸体内外诱导鼠胚胎心肌细胞凋亡的研究[J]. 中国生育健康杂志, 2002, 13(4): 173-176. DOI: 10.3969/j.issn.1671-878X.2002.04.016.
	Lie OV, Bennett GD, Rosenquist TH. The N-methyl-d-aspartate receptor in heart development: a gene knockdown model using siRNA[J]. Reprod Toxicol, 2010, 29(1): 32-41. PMID: 19737608. PMCID: PMC2818120. DOI: 10.1016/j.reprotox.2009.08.005.
	Yamagishi H. Cardiac neural crest[J]. Cold Spring Harb Perspect Biol, 2021, 13(1): a036715. PMID: 32071091. PMCID: PMC7778148. DOI: 10.1101/cshperspect.a036715.