Nataša Karas Kuželički, Alenka Šmid, Maša Vidmar Golja, Tina Kek, Andreja Eberlinc, Borut Geršak, Uroš Mazič, Irena Mlinarič-Raščan, Ksenija Geršak
{"title":"与未受影响的兄弟姐妹相比,口唇裂和先天性心脏缺陷患儿叶酸和蛋氨酸循环基因中常见多态性的发生率更高。","authors":"Nataša Karas Kuželički, Alenka Šmid, Maša Vidmar Golja, Tina Kek, Andreja Eberlinc, Borut Geršak, Uroš Mazič, Irena Mlinarič-Raščan, Ksenija Geršak","doi":"10.1002/bdr2.2408","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Uninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one-carbon-activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD-affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD-affected and unaffected siblings.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Only the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the <i>FPGS</i> gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate–methionine cycles.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Both OFC and CHD formation were associated with a higher number of mutated loci in genes of folate–methionine cycles, indicating polygenic and possibly multifactorial inheritance.</p>\n </section>\n </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"116 11","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2408","citationCount":"0","resultStr":"{\"title\":\"Higher Incidence of Common Polymorphisms in the Genes of Folate and Methionine Cycles in Children With Orofacial Clefs and Congenital Heart Defects Compared to their Unaffected Siblings\",\"authors\":\"Nataša Karas Kuželički, Alenka Šmid, Maša Vidmar Golja, Tina Kek, Andreja Eberlinc, Borut Geršak, Uroš Mazič, Irena Mlinarič-Raščan, Ksenija Geršak\",\"doi\":\"10.1002/bdr2.2408\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Uninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one-carbon-activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD-affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD-affected and unaffected siblings.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Only the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the <i>FPGS</i> gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate–methionine cycles.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Both OFC and CHD formation were associated with a higher number of mutated loci in genes of folate–methionine cycles, indicating polygenic and possibly multifactorial inheritance.</p>\\n </section>\\n </div>\",\"PeriodicalId\":9121,\"journal\":{\"name\":\"Birth Defects Research\",\"volume\":\"116 11\",\"pages\":\"\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2408\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Birth Defects Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2408\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Birth Defects Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2408","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
Higher Incidence of Common Polymorphisms in the Genes of Folate and Methionine Cycles in Children With Orofacial Clefs and Congenital Heart Defects Compared to their Unaffected Siblings
Background
Uninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one-carbon-activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus.
Methods
We used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD-affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD-affected and unaffected siblings.
Results
Only the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the FPGS gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate–methionine cycles.
Conclusions
Both OFC and CHD formation were associated with a higher number of mutated loci in genes of folate–methionine cycles, indicating polygenic and possibly multifactorial inheritance.
期刊介绍:
The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks.
Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.