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

Karas Kuželički, Nataša (author), Šmid, Alenka (author), Vidmar, Maša (author), Kek, Tina (author), Eberlinc, Andreja (author), Geršak, Borut (author), Mazić, Uroš (author), Mlinarič-Raščan, Irena (author), Geršak, Ksenija (author)

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.

• Language: English
• Keywords: congenital heart disease, folate metabolism, FPGS, genetics, orofacial clefts, polymorphisms, sibling pairs
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 11 str.
• Numbering: Vol. 116, iss. 11, art. e2408
• PID: 20.500.12556/RUL-164608
• UDC: 575:616.12-039
• ISSN on article: 2472-1727
• DOI: 10.1002/bdr2.2408
• COBISS.SI-ID: 213546755
• Publication date in RUL: 05.11.2024

Record is a part of a journal

• Title: Birth defects research
• Shortened title: Birth defects res.
• Publisher: Wiley
• ISSN: 2472-1727
• COBISS.SI-ID: 530027289

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: prirojena srčna napaka, metabolizem folatov, FPGS, orofacialne razjede, polimorfizmi, bratje in sestre pari, genetika, srčne napake