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

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.

• Jezik: Angleški jezik
• Ključne besede: congenital heart disease, folate metabolism, FPGS, genetics, orofacial clefts, polymorphisms, sibling pairs
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 11 str.
• Številčenje: Vol. 116, iss. 11, art. e2408
• PID: 20.500.12556/RUL-164608
• UDK: 575:616.12-039
• ISSN pri članku: 2472-1727
• DOI: 10.1002/bdr2.2408
• COBISS.SI-ID: 213546755
• Datum objave v RUL: 05.11.2024

Gradivo je del revije

• Naslov: Birth defects research
• Skrajšan naslov: Birth defects res.
• Založnik: Wiley
• ISSN: 2472-1727
• COBISS.SI-ID: 530027289

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: prirojena srčna napaka, metabolizem folatov, FPGS, orofacialne razjede, polimorfizmi, bratje in sestre pari, genetika, srčne napake