Prevalence and clinical significance of the mtr gene a2756g polymorphism in congenital pathology in newborns
Received: 2026-02-11 14:36:46
Published: 2026-04-30
Abstract
Aim. To investigate the distribution frequency and evaluate the association of MTR gene polymorphic variants (Asp919Gly, rs1805087) in newborns with congenital malformations (CMs).
Materials and Methods. The study included 113 newborns with CMs (main group), subdivided into three clinical subgroups: folate-dependent CMs (n=75), folate-independent CMs (n=21), and CMs associated with chromosomal abnormalities (n=17), as well as 110 healthy newborns (control group). Genotyping was performed using real-time polymerase chain reaction (RT-PCR).
Results. The frequency of the minor Gly allele in the main group (35.84%) was significantly higher than that in the control group (21.36%). The most pronounced differences were observed in the subgroup with folate-dependent CMs, where the Gly allele frequency reached 40.67%, and the homozygous Gly/Gly genotype was detected in 21.33% of cases compared with 7.27% in the control group (χ²=7.8; p=0.01; OR=3.46; 95% CI: 1.45–8.26). Hardy–Weinberg equilibrium analysis demonstrated a significant deviation in the main group (χ²=5.03; p=0.028), with a deficiency of heterozygotes (D=−0.21). No significant associations between the MTR A2756G polymorphism and folate-independent CMs or CMs associated with chromosomal abnormalities were identified. The Gly/Gly genotype demonstrated high specificity (SP=0.93) and an area under the ROC curve (AUC=0.57) as a marker of folate-dependent CMs.
Conclusion. The findings suggest that the MTR Asp919Gly polymorphism may serve as a potential molecular genetic marker of susceptibility to folate-dependent congenital malformations in newborns.
Keywords
List of references
-
Bai Z., Zhang J., Zhang Z. et al. Global, regional, and national burden of congenital birth defects, 1990–2021: an analysis of the Global Burden of Disease Study 2021. EClinicalMedicine. 2024.
-
Lee K.S., Choi Y.J., Cho J., Lee H., Lee H., Park S.J. et al. Environmental and genetic risk factors of congenital anomalies: an umbrella review of systematic reviews and meta-analyses. Journal of Korean Medical Science. 2021;36(28):e183. https://doi.org/10.3346/jkms.2021.36.e183.
-
Moges N., Belay D.B., Gebeyehu N.A. et al. The effect of folic acid intake on congenital anomalies: a systematic review and meta-analysis. Scientific Reports. 2024;14.
-
Liu C., Liu C., Wang Q., Zhang Z. Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis. Archives of Gynecology and Obstetrics. 2021;303:463–471.
-
Raina J.K., Sharma M., Panjaliya R.K. Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population: a case-control study encompassing meta-analysis and trial sequential analysis. BMC Pediatrics. 2022;22:179. https://doi.org/10.1186/s12887-022-03227-z.
-
Liu W., Wang J., Chen L.J. Association between MTR A2756G polymorphism and susceptibility to congenital heart disease: a meta-analysis. PLoS ONE. 2022;17(7):e0270828. https://doi.org/10.1371/journal.pone.0270828.
-
Liu Y., Zhong T., Song X., Zhang S., Sun M., Wei J., Shu J., Yang T., Wang T., Qin J. Association of MTR gene polymorphisms with the occurrence of non-syndromic congenital heart disease: a case-control study. Scientific Reports. 2023;13:9424. https://doi.org/10.1038/s41598-023-36330-x.
-
Almekkawi A.K., AlJardali M.W., Daadaa H.M. et al. Folate pathway gene single nucleotide polymorphisms and neural tube defects: a systematic review and meta-analysis. Journal of Personalized Medicine. 2022;12(10):1609. https://doi.org/10.3390/jpm12101609.
-
Karas Kuzˇelicˇki N., Doljak B. Congenital heart disease and genetic changes in folate/methionine cycles. Genes. 2024;15(7):872. https://doi.org/10.3390/genes15070872.
-
Viswanathan M., Urrutia R.P., Hudson K.N. et al. Folic acid supplementation to prevent neural tube defects: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2023;330(5):460–466. https://doi.org/10.1001/jama.2023.9864.
-
Crider K.S., Qi Y.P., Devine O., Tinker S.C., Berry R.J. Folic acid and the prevention of birth defects: 30 years of opportunity and controversies. Annual Review of Nutrition. 2022;42:423–452.
-
Abate B.B., Sendek A., Wudu M. et al. Preconception folic acid and multivitamin supplementation for the prevention of neural tube defects: an umbrella review of systematic reviews and meta-analyses. Clinical Nutrition ESPEN. 2024.
-
Sun M., Chen Y., Li P. et al. Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring. BMC Cardiovascular Disorders. 2021;21:272. https://doi.org/10.1186/s12872-021-02117-z.
-
Liu H., Ou J., Chen Y. et al. Association of maternal folate intake and offspring MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease. Nutrients. 2023;15(16):3502. https://doi.org/10.3390/nu15163502.
-
Nie X., Chen Y., Chen Y. et al. Assessment of evidence on reported non-genetic risk factors of congenital heart defects: an umbrella review. BMC Pregnancy and Childbirth. 2022;22:371. https://doi.org/10.1186/s12884-022-04600-7.
-
de la Fournie`re B., Dhombres F., Maurice P. et al. Prevention of neural tube defects by folic acid supplementation: a national population-based study. Nutrients. 2020;12(10):3170. https://doi.org/10.3390/nu12103170.
-
Liu H., Wang B., Zhang Y. et al. Maternal folic acid supplementation, genetic variants in folate metabolism and the risk of congenital heart disease in offspring: a case-control study. Nutrients. 2022;14.
-
Gulmukhamedov PB. Assessment of the role of the MTR gene polymorphic variant (A2756G) in the mechanisms underlying the development of congenital maxillofacial malformations. Yangi O‘zbekiston, Yangi Tadqiqotlar Jurnali. 2026;5(2). Published June 17, 2026. In Russian.
-
Efremova OA. Investigation of the role of interlocus interactions between folate cycle genes and matrix metalloproteinase genes in the development of fetal growth restriction. Research Results in Biomedicine. 2022;8(1):36–55. https://doi.org/10.18413/2658-6533-2022-8-1-0-3. In Russian.
-
Strozenko LA, Ponomarev VS, Lobanov YuF, Dorokhov NA, Sukmanova IA, Shevchenko KI, Skudarnov EV, Sanina OO. Polymorphic variants of folate cycle genes as predictors of hyperhomocysteinemia. Russian Pediatric Journal. 2024;27(1):34–39. In Russian.
-
Gladkikh ES, Shcherbak VA. Current concepts of the effects of hyperhomocysteinemia on pregnant women and newborns. Bulletin of the Smolensk State Medical Academy. 2025;24(1):123–130. https://doi.org/10.37903/vsgma.2025.1.18. In Russian.
-
Ivanov AM, Gilmanov AZh, Malyutina NN, Khovaeva YaB, Nenasheva OYu, Elkin GI, Sosnin DYu. Folate cycle gene polymorphisms as a risk factor for the development of hyperhomocysteinemia. Health Risk Analysis. 2020;(4):137–146. https://doi.org/10.21668/health.risk/2020.4.16. InRussian.
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