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The Association Between MTHFR C677T Gene Polymorphism and Repeated Pregnancy Loss in Arabic Countries: a Systematic Review and Meta-Analysis

  • Genetics: Review
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Abstract

The role of MTHFR C677T polymorphism in repeated pregnancy loss (RPL) among different populations has been studied with inconsistent results. The study objective was to determine the association between MTHFR C677T polymorphisms and RPL among Arab women. The review included all the available studies investigating the association between MTHFR C677T polymorphism and RPL from 2000 until now. The searched database included Cochrane, Trip, EMBASE, and Google Scholar. Two authors independently reviewed the searched articles for eligibility, judged their risk of bias, and extracted the characteristics of the studies. Review Manager 5.3 program was used for data analysis using odds ratio (OR) at a 95% confidence interval (CI). The study revealed a statistically significant difference between cases and controls regarding combined MTHFR C677T polymorphisms (OR = 1.50, 95% CI = 1.15–1.96), MTHFR C677T heterozygous (OR = 1.41, 95% CI = 1.08–1.83), and MTHFR C677T homozygous (OR = 4.19, 95% CI = 1.87–9.39). Considerable significant heterogeneity was recorded in the three analyses (P < 0.05). The review supported the hypothesis that MTHFR C677T mutation is considered a significant risk factor for RPL among Arab women.

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Data Availability

The data that support the findings of this study were derived from the following resources available in scientific journals:

- Osman OM, Abulata NN. Inherited thrombophilia and early recurrent pregnancy loss among Egyptian women. Open Journal of Obstetrics and Gynecology. 2015 May 6;5(05):251 (available at http://dx.doi.org/10.4236/ojog.2015.55037).

- Mohamed MA, El Moaty MA, El Kholy AF, Mohamed SA, Ali AI. Thrombophilic gene mutations in women with repeated spontaneous miscarriage. Genetic testing and molecular biomarkers. 2010 Oct 1;14(5):593–7 (available at https://doi.org/10.1089/gtmb.2010.0052).

- Settin A, Elshazli R, Salama A, ElBaz R. Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian women with unexplained recurrent pregnancy loss. Genetic Testing and Molecular Biomarkers. 2011 Dec 1;15(12):887–92 (available at https://doi.org/10.1089/gtmb.2011.0049).

- Badawy A, AlSel BA, Fawzy MS. Factor V Leiden G1691A and Prothrombin G20210A mutations are associated with repeated spontaneous miscarriage in Northern area of Saudi Arabia. Genetics and Molecular Research. 2017 Oct 21;16(4) (available at http://dx.doi.org/10.4238/gmr16039810).

- Al-Achkar W, Wafa A, Ammar S, Moassass F, Jarjour RA. Association of methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms with recurrent pregnancy loss in Syrian women. Reproductive Sciences. 2017 Sep;24(9):1275–9 (available at https://doi.org/10.1177/1933719116682874).

- Gawish G. The Prevalence of inherited thrombophilic polymorphisms in Saudi females with recurrent pregnancy loss confirmed using different screening protocols of PCR. J Mol Genet Med. 2015;9(156):1747 (available at https://scholar.googleusercontent.com/scholar?q=cache:LFnDdeoWdjoJ:scholar.google.com/&hl=en&as_sdt=0,5).

- Alkhuriji A, Alraqibah AA, Alharbi AA, Babay Z, Al-Mukaynizi FB, Althomali A, Abdel-Razeq SS, Warsy AS. Two polymorphisms in methylenetetrahydrofolate reductase gene (C677T and A1298C) frequently associated with recurrent spontaneous abortion show no association in Saudi women. Biocell. 2020;44(4):613 (available at https://doi.org/10.32604/biocell.2020.09652).

- Babker AM, Gameel FE, Monwara K. Methylenetetrahydrofolate reductase c677t polymorphism in Sudanese women with recurrent spontaneous abortions. Kuwait Med J. 2016 Jun 1;48(2):100–4 (available at https://www.cabdirect.org/globalhealth/abstract/20163184274).

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Acknowledgements

The researchers would like to thank Dr. Yousef Almutairi (Saudi Ministry of Health, Riyadh, Saudi Arabia) for his assistance in reviewing the manuscript.

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Author notes

  1. Amjad Alfaleh and Abdullah Alkattan contributed equally to this work.

Authors and Affiliations

  1. Research and Planning Unit, General Directorate of School Health, Ministry of Health, Riyadh, Saudi Arabia

    Amjad Alfaleh & Abdullah Alkattan

  2. Department of Research, Assisting Deputyship for Primary Health Care, Ministry of Heath, Riyadh, Saudi Arabia

    Nagla Mahmoud, Amjad Alanazi & Nashwa Radwan

  3. Department of Family Medicine, Quizah Primary Healthcare Center, Ministry of Heath, Jeddah, Saudi Arabia

    Fatimah Alfaleh

  4. Urology Department, Al-Iman General Hospital, Ministry of Heath, Riyadh, Saudi Arabia

    Nasser Almutair

  5. Department of Public Health and Community Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt

    Ibrahim Kbbash & Nashwa Radwan

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Correspondence to Amjad Alfaleh or Abdullah Alkattan.

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Alfaleh, A., Alkattan, A., Mahmoud, N. et al. The Association Between MTHFR C677T Gene Polymorphism and Repeated Pregnancy Loss in Arabic Countries: a Systematic Review and Meta-Analysis. Reprod. Sci. 30, 2060–2068 (2023). https://doi.org/10.1007/s43032-023-01201-3

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