open access

Vol 90, No 2 (2019)
Research paper
Published online: 2019-02-28
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MTHFR genetic polymorphism and the risk of intrauterine fetal death in Polish women

Hubert Wolski12, Grazyna Kurzawinska23, Krzysztof Drews23, Magdalena Barlik23, Przemyslaw Kadziolka4, Zbyszko Malewski2, Paula Mikolajska-Ptas1, Michal Bylewski1, Agnieszka Seremak-Mrozikiewicz23
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Pubmed: 30860273
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Ginekol Pol 2019;90(2):76-81.
Affiliations
  1. Division of Gynecology and Obstetrics, Podhale Multidisciplinary Hospital, Nowy Targ, Poland
  2. Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poland
  3. Laboratory of Molecular Biology in Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poland
  4. Department of Maternal and Child Health, Poznan University of Medical Sciences, Poland

open access

Vol 90, No 2 (2019)
ORIGINAL PAPERS Gynecology
Published online: 2019-02-28

Abstract

Objectives: To evaluate the role of MTHFR genetic variants in the etiology of intrauterine fetal death in the second part of pregnancy at women from Polish population. 

Material and methods: A case-control study was performed on a 76 women with a positive history of at least one in- trauterine fetal death after 22 gestational week and 400 healthy controls. The MTHFR genotyping for polymorphic sites 667C > T, 1298A > C, 1793G > A was determined by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method. 

Results: For 1298A > C polymorphism, no statistically significant higher frequency of AA vs. AC+CC genotype was observed in the IUFD group 67.1 % vs. 55.2% in the control group (OR = 0.61, p = 0.05, pcorr = 0.15). We observed overrepresentation of three-locus haplotype CCG (p = 0.20; pcorr = 0.56) and two-locus haplotype CC (p = 0.17; pcorr = 0.48) in the IUFD group compared to controls. 

Conclusions: There was no observed relationships in genotype frequency of MTHFR 677C > T and 1793G > A variants, however 1298A > C showed a slightly higher but statistically insignificant prevalence in IUFD compared to the controls in Polish population. Further studies on a larger population are needed. 

Abstract

Objectives: To evaluate the role of MTHFR genetic variants in the etiology of intrauterine fetal death in the second part of pregnancy at women from Polish population. 

Material and methods: A case-control study was performed on a 76 women with a positive history of at least one in- trauterine fetal death after 22 gestational week and 400 healthy controls. The MTHFR genotyping for polymorphic sites 667C > T, 1298A > C, 1793G > A was determined by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method. 

Results: For 1298A > C polymorphism, no statistically significant higher frequency of AA vs. AC+CC genotype was observed in the IUFD group 67.1 % vs. 55.2% in the control group (OR = 0.61, p = 0.05, pcorr = 0.15). We observed overrepresentation of three-locus haplotype CCG (p = 0.20; pcorr = 0.56) and two-locus haplotype CC (p = 0.17; pcorr = 0.48) in the IUFD group compared to controls. 

Conclusions: There was no observed relationships in genotype frequency of MTHFR 677C > T and 1793G > A variants, however 1298A > C showed a slightly higher but statistically insignificant prevalence in IUFD compared to the controls in Polish population. Further studies on a larger population are needed. 

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Keywords

intrauterine fetal death; MTHFR; genetic polymorphism

About this article
Title

MTHFR genetic polymorphism and the risk of intrauterine fetal death in Polish women

Journal

Ginekologia Polska

Issue

Vol 90, No 2 (2019)

Article type

Research paper

Pages

76-81

Published online

2019-02-28

Page views

1663

Article views/downloads

1485

DOI

10.5603/GP.2019.0013

Pubmed

30860273

Bibliographic record

Ginekol Pol 2019;90(2):76-81.

Keywords

intrauterine fetal death
MTHFR
genetic polymorphism

Authors

Hubert Wolski
Grazyna Kurzawinska
Krzysztof Drews
Magdalena Barlik
Przemyslaw Kadziolka
Zbyszko Malewski
Paula Mikolajska-Ptas
Michal Bylewski
Agnieszka Seremak-Mrozikiewicz

References (26)
  1. Lamont K, Scott NW, Jones GT, et al. Risk of recurrent stillbirth: systematic review and meta-analysis. BMJ. 2015; 350: h3080.
  2. Man J, Hutchinson JC, Heazell AE, et al. Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death. Ultrasound Obstet Gynecol. 2016; 48(5): 579–584.
  3. Stillbirth Collaborative Research Network Writing Group. Association between stillbirth and risk factors known at pregnancy confirmation. JAMA. 2011; 306(22): 2469–2479.
  4. Man J, Hutchinson JC, Ashworth M, et al. Stillbirth and intrauterine fetal death: role of routine histological organ sampling to determine cause of death. Ultrasound Obstet Gynecol. 2016; 48(5): 596–601.
  5. Barut MU, Bozkurt M, Kahraman M, et al. Thrombophilia and Recurrent Pregnancy Loss: The Enigma Continues. Med Sci Monit. 2018; 24: 4288–4294.
  6. Kim JiY, Kim JiW, Sung SeRa, et al. Impact of RFC1, MTHFR, and MTHFD1 polymorphism on unexplained pregnancy loss (UPL): comparative analysis of maternal and fetal components using mother-abortus paired samples. Eur J Obstet Gynecol Reprod Biol. 2018; 231: 152–157.
  7. van der Put NM, Gabreëls F, Stevens EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5): 1044–1051.
  8. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10(1): 111–113.
  9. Hanson NQ, Aras O, Yang F, et al. C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease. Clin Chem. 2001; 47(4): 661–666.
  10. González JR, Armengol L, Guinó E et al., (2014). SNPassoc: SNPs-based whole genome association studies. R package version 1.9-2. https://CRAN.R-project.org/package=SNPassoc.
  11. Drews K, Różycka A, Barlik M, et al. Polymorphic variants of genes involved in choline pathway and the risk of intrauterine fetal death. Ginekol Pol. 2017; 88(4): 205–211.
  12. Seremak-Mrozikiewicz A, Barlik M, Różycka A, et al. Importance of polymorphic variants of phosphatidylethanolamine N-methyltransferase (PEMT) gene in the etiology of intrauterine fetal death in the Polish population. Eur J Obstet Gynecol Reprod Biol. 2018; 231: 43–47.
  13. Turgal M, Gumruk F, Karaagaoglu E, et al. Methylenetetrahydrofolate Reductase Polymorphisms and Pregnancy Outcome. Geburtshilfe Frauenheilkd. 2018; 78(9): 871–878.
  14. Simonidesova M, Simko J, Holoman K. Defects of genes encoding inhibitors of coagulation and their application in early miscarriage aetiology. Bratisl Lek Listy. 2014; 115(11): 730–735.
  15. Torabi R, Zarei S, Zeraati H, et al. Combination of thrombophilic gene polymorphisms as a cause of increased the risk of recurrent pregnancy loss. J Reprod Infertil. 2012; 13(2): 89–94.
  16. Nurk E, Tell GS, Refsum H, et al. Factor V Leiden, pregnancy complications and adverse outcomes: the Hordaland Homocysteine Study. QJM. 2006; 99(5): 289–298.
  17. Silver RM, Saade GR, Thorsten V, et al. Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth: the Stillbirth Collaborative Research Network. Am J Obstet Gynecol. 2016; 215(4): 468.e1–468.e17.
  18. Murakami S, Matsubara N, Saitoh M, et al. The relation between plasma homocysteine concentration and methylenetetrahydrofolate reductase gene polymorphism in pregnant women. J Obstet Gynaecol Res. 2001; 27(6): 349–352.
  19. Hefler L, Jirecek S, Heim K, et al. Genetic polymorphisms associated with thrombophilia and vascular disease in women with unexplained late intrauterine fetal death: a multicenter study. J Soc Gynecol Investig. 2004; 11(1): 42–44.
  20. Aytekin E, Ergun SG, Ergun MA, et al. Evaluation of GenoFlow Thrombophilia Array Test Kit in its detection of mutations in Factor V Leiden (G1691A), prothrombin G20210A, MTHFR C677T and A1298C in blood samples from 113 Turkish female patients. Genet Test Mol Biomarkers. 2014; 18(11): 717–721.
  21. Le Marchand L, Donlon T, Hankin JH, et al. B-vitamin intake, metabolic genes, and colorectal cancer risk (United States). Cancer Causes Control. 2002; 13(3): 239–248.
  22. Zetterberg H, Regland B, Palmér M, et al. Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos. Eur J Hum Genet. 2002; 10(2): 113–118.
  23. Aracic N, Roje D, Jakus IA, et al. The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome. Yonsei Med J. 2016; 57(5): 1230–1235.
  24. Jin H, Cheng H, Chen W, et al. An evidence-based approach to globally assess the covariate-dependent effect of the MTHFR single nucleotide polymorphism rs1801133 on blood homocysteine: a systematic review and meta-analysis. Am J Clin Nutr. 2018; 107(5): 817–825.
  25. Ibrahim S, Maqbool S, Azam M, et al. CBS mutations and MTFHR SNPs causative of hyperhomocysteinemia in Pakistani children. Mol Biol Rep. 2018; 45(3): 353–360.
  26. Li A, Shi Y, Xu L, et al. A possible synergistic effect of MTHFR C677T polymorphism on homocysteine level variations increased risk for ischemic stroke. Medicine (Baltimore). 2017; 96(51): e9300.

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