20.500.12556/RUL-164608 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. congenital heart disease folate metabolism FPGS genetics orofacial clefts polymorphisms sibling pairs prirojena srčna napaka metabolizem folatov FPGS orofacialne razjede polimorfizmi bratje in sestre pari genetika srčne napake true false true Angleški jezik Slovenski jezik Članek v reviji 2024-11-05 12:40:03 2024-11-05 12:40:09 2024-11-22 14:55:01 0000-00-00 00:00:00 2024 0 0 11 str. iss. 11, art. e2408 Vol. 116 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575:616.12-039 2472-1727 10.1002/bdr2.2408 213546755 Birth_Defects_Research_-_2024_-_Karas Kuzelicki_-_Higher_Incidence_of_Common_Polymorphisms_in_the_Genes_of_Folate_and.pdf Birth_Defects_Research_-_2024_-_Karas Kuzelicki_-_Higher_Incidence_of_Common_Polymorphisms_in_the_Genes_of_Folate_and.pdf 1 A00D9C0CC4FADFCDA882BE1FD9B1D7EB f37965fd1685c6dd7a35c2751d3936cd588b81f466ef328d918ad50f8913d20d bcbf47be-9b6a-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195161 https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2408 1 60ffdb24-9b6a-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195160 Fakulteta za farmacijo Medicinska fakulteta 0 0 0