بررسی ارتباط پلی‌مورفیسم‌های شایع تک‎نوکلئوتیدی در ترومبوفیلی ارثی با سقط مکرر در جمعیت زنان ایران: یک مرور روایتی

نوع مقاله : مروری

نویسندگان

1 دانشیار گروه مامایی، دانشکده پرستاری و مامایی، دانشگاه علوم پزشکی اردبیل، اردبیل، ایران.

2 کارشناس ارشد مامایی، دانشکده پرستاری و مامایی، دانشگاه علوم پزشکی اردبیل، اردبیل، ایران. کمیته تحقیقات دانشجویی، دانشکده پرستاری و مامایی، دانشگاه علوم پزشکی اردبیل، اردبیل، ایران.

3 استادیار گروه مامایی، دانشکده پرستاری و مامایی، دانشگاه علوم پزشکی اردبیل، اردبیل، ایران.

4 دانشیار گروه ژنتیک پزشکی و پاتولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی اردبیل، اردبیل، ایران.

10.22038/ijogi.2025.89944.6507

چکیده

مقدمه: سقط مکرر به‌عنوان از دست دادن 2 یا بیش از 2 بارداری پیش از هفته ۲۰ بارداری تعریف می‌شود. این عارضه می‌تواند ناشی از علل مختلفی از جمله عوامل ژنتیکی، ایمونولوژیک و ساختاری باشد؛ با این‌حال، تقریباً در ۵۰% از موارد، علت مشخصی یافت نمی‌شود. در میان عوامل احتمالی، نقش پلی‌مورفیسم‌های ترومبوفیلی ارثی به‌عنوان یکی از زمینه‌سازهای سقط مکرر، موضوعی چالش‌برانگیز باقی‌مانده است. مطالعه مروری حاضر با هدف بررسی ارتباط پلی‎ مورفیسم‎های شایع تک‎ نوکلئوتیدی در ترومبوفیلی ارثی با سقط مکرر در جمعیت زنان ایران انجام شد.
روش‌کار: در این مطالعه مروری با استفاده از کلیدواژه‌های "thrombophilia"، "recurrent pregnancy loss"، "Single Nucleotide Polymorphism"، "MTHFR polymorphism"، "recurrent miscarriage"، "Prothrombin G20210A"، "PAI-1 polymorphism"، "Factor XIII V34L"، و "Iran"، تمام مقالات فارسی و انگلیسی که در بازه زمانی ۲۰۰۸ تا ۲۰۲۵ میلادی به بررسی ارتباط بین پلی‎مورفیسم‌های تک‌نوکلئوتیدی شایع ترومبوفیلی ارثی و سقط مکرر در جمعیت ایرانی پرداخته بودند، مورد بررسی قرار گرفتند.
یافته­ها: در جستجوی اولیه، ۷۸۸ مطالعه شناسایی شد که پس از غربالگری بر اساس عناوین، چکیده‌ها و ارزیابی متن کامل مقالات و با در نظر گرفتن معیارهای ورود و خروج، در نهایت ۲۳ مقاله برای استخراج داده‌ها انتخاب شدند. در حالی که شواهد مربوط به ارتباط پلی‌مورفیسم‌های FVL G1691A و FII G20210A با سقط مکرر در جمعیت ایران ناهمگون است، پلی‌مورفیسم‌های ژن MTHFR و PAI-1 4G/4G ارتباط قوی‌تری را در مطالعات مختلف نشان داده‌اند.
نتیجه­ گیری: مرور شواهد موجود در ایران نشان داد که پلی‌مورفیسم‌های MTHFR و PAI‑1 4G/4G احتمالاً با افزایش خطر سقط مکرر در ارتباط هستند، در حالی ‌که شواهد مربوط به FVL G1691A و FII G20210A ناهمگون بوده و برای FXIII V34L عمدتاً ارتباط معناداری گزارش نشده بود. این یافته‌ها بر لزوم انجام مطالعات استانداردتر و مبتنی بر جمعیت‌های بزرگ‌تر تأکید دارد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Association of Common Single Nucleotides Polymorphisms within Inherited Thrombophilia with Recurrent Pregnancy Loss in Female Population of Iran: A Narrative Review

نویسندگان [English]

  • Samira Shahbazzadeghan 1
  • Neda Farzizadeh 2
  • Farideh Mostafazadeh 3
  • Behzad Davarnia 4
1 Associate Professor, Department of Midwifery, School of Nursing and Midwifery, Ardabil University of Medical Sciences, Ardabil, Iran.
2 M.Sc. of Midwifery, School of Nursing and Midwifery, Ardabil University of Medical Sciences, Ardabil, Iran. Students Research Committee, School of Nursing and Midwifery, Ardabil University of Medical Sciences, Ardabil, Iran.
3 Assistant Professor, Department of Midwifery, School of Nursing and Midwifery, Ardabil University of Medical Sciences, Ardabil, Iran.
4 Associate Professor, Department of Medical Genetics and Pathology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
چکیده [English]

Introduction: Recurrent pregnancy loss is defined as at least two pregnancy losses up to 20 weeks of pregnancy. Various genetic, immunologic, and anatomic etiologies lead to recurrent pregnancy loss; however, about 50% of them remain idiopathic. Among the possible causes, the role of different inherited thrombophilia polymorphisms as one of the effective factors in recurrent pregnancy loss still remains unclear. The present review study was conducted with aim to investigate the association of common single nucleotide polymorphisms in hereditary thrombophilia with recurrent pregnancy losses in female population of Iran.
Methods: In this review study, using keywords including “Thrombophilia”, “Recurrent pregnancy loss”, “Recurrent miscarriage”, “Single Nucleotide Polymorphism”, “MTHFR polymorphism”, “Prothrombin G20210A”, “PAI-1 polymorphism”, “Factor XIII V34L”, and “Iran”, all articles in English or Persian investigating the association between common single nucleotide polymorphisms within inherited thrombophilia and recurrent pregnancy loss in female population of Iran from 2008 to 2025 were evaluated.
Results: In the initial search, 788 results were found. Following the screening based on the titles, abstracts, and full texts according to the inclusion and exclusion criteria, finally, 23 articles remained for the data extraction. The results showed that while there was no consistent evidence for FVL G1691A and FII G20210A polymorphisms in the Iranian population, MTHFR and PAI-1 4G/4G gene polymorphisms showed more consistent association in the studies.
Conclusion: A review of the available evidence in Iran showed that the MTHFR and PAI-1 4G/4G polymorphisms are likely to be associated with an increased risk of recurrent pregnancy loss, while the evidence for FVL G1691A and FII G20210A was inconsistent, and for FXIII V34L, a significant association was mostly not reported. These findings emphasize the need for more standardized studies based on larger populations.

کلیدواژه‌ها [English]

  • PAI-1
  • Recurrent Pregnancy Loss
  • Single Nucleotide Polymorphism
  • Thrombophilia

مراجع

  1. Liu C, Wei X, Wang F. The predictive value of ultrasound markers for pregnancy outcomes in recurrent pregnancy loss: a retrospective study. Scientific Reports 2024; 14(1):16657.
  2. Babaei K, Aziminezhad M, Mirzajani E, Mozdarani H, Sharami SH, Norollahi SE, et al. A critical review of the recent concept of regulatory performance of DNA Methylations, and DNA methyltransferase enzymes alongside the induction of immune microenvironment elements in recurrent pregnancy loss. Toxicology Reports 2024; 12:546-63.
  3. Seyedoshohadaei F, Blooryan P, Rahmani Kh. The Effect of Enoxaparin and Aspirin in Preventing Miscarriage in Women with Polycystic Ovary Syndrome with a History of Two or More Recurrent Abortion without Acquired Thrombophilia. Iran J Obstet Gynecol Infertil 2025; 28(4):10-18.
  4. Rasmark Roepke E, Matthiesen L, Rylance R, Christiansen OB. Is the incidence of recurrent pregnancy loss increasing? A retrospective register‐based study in Sweden. Acta obstetricia et gynecologica Scandinavica 2017; 96(11):1365-72.
  5. Berek JS. Berek & Novak's gynecology. 16nd Lippincott Williams & Wilkins; 2019.
  6. Cunningham FG, Leveno KJ, Dashe JS, Hoffman BL, Spong CY, Casey BM, et al. Williams Obstetrics. 16nd ed. New York: McGraw-Hill Education; 2022.
  7. Nouri N, Ghasemi HF, Dehghan J, Ghasemi M. Frequency of various factors affecting pregnancy loss in patients with history of recurrent pregnancy loss in Sistan and Balouchestan province, 2017-2018. Iran J Obstet Gynecol Infertil 2023; 26(3):16-24.
  8. He X, Chen Q. Reduced expressions of connexin 43 and VEGF in the first-trimester tissues from women with recurrent pregnancy loss. Reproductive Biology and Endocrinology 2016; 14(1):46.
  9. Sonehara K, Yano Y, Naito T, Goto S, Yoshihara H, Otani T, et al. Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss. Nature communications 2024; 15(1):5744.
  10. Cuadrado-Torroglosa I, García-Velasco JA, Alecsandru D. Maternal–Fetal Compatibility in Recurrent Pregnancy Loss. Journal of Clinical Medicine 2024; 13(8):2379.
  11. Ronald SG, Beth YK, Arthur FH, Ingrid EN. Danforth's obstetrics and gynecology. 10nd Lippincott Williams and Wilkins 2008; 257:67.
  12. Basha A, Alkhatib Y, Tashtoush T, Yousef M, Oweidi L, Alkhatib M, et al. Recurrent early pregnancy loss and congenital thrombophilia: A prospective study. Journal of Clinical Medicine 2024; 13(22):6871.
  13. Khalife S, Geitani R. Association of inherited thrombophilia with recurrent pregnancy loss in a population of lebanese women: a case control study. International Journal of Fertility & Sterility 2022; 16(3):247.
  14. Bagheri R, ali Rahmani S, Khoramifar L, Ilkhichoui S. Study of common chromosomal abnormalities and Plasminogen activator Inhibitor (PAI-1) gene Polymorphism (5G/4G) and Prothrombin (F2) gene mutation (G20210A) in women with recurrent abortions in the North West of Iran. Medical Journal of Tabriz University of Medical Sciences 2021; 43(5):400-9.
  15. Kamali M, Hantoushzadeh S, Borna S, Neamatzadeh H, Mazaheri M, Noori-Shadkam M, et al. Association between thrombophilic genes polymorphisms and recurrent pregnancy loss susceptibility in the Iranian population: a systematic review and meta-analysis. Iranian biomedical journal 2018; 22(2):78.
  16. Jung JH, Kim JH, Song GG, Choi SJ. Association of the F13A1 Val34Leu polymorphism and recurrent pregnancy loss: A meta-analysis. European Journal of Obstetrics & Gynecology and Reproductive Biology 2017; 215:234-40.
  17. Chen H, Nie S, Lu M. Association between plasminogen activator inhibitor‐1 gene polymorphisms and recurrent pregnancy loss: a systematic review and meta‐analysis. American Journal of Reproductive Immunology 2015; 73(4):292-300.
  18. Yousefian M, Angaji SA, Siasi E, Rahmani SA, Abbasalizadeh Khiaban S. Association of polymorphisms of F2 (rs3136520) and PAI-1 (rs6090) Genes with recurrent pregnancy loss in Iranian Azeri women. Avicenna Journal of Clinical Medicine 2021; 28(2):118-25.
  19. Najjar AA, Hassouna I, Srour MA, Ibrahim HM, Assi RY, Abd El Latif HM. Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage. Thrombosis Journal 2024; 22(1):20.
  20. Shi YL, Zhao J, Ai FL, Wang YT, Hu KR, Wang XW, et al. Evaluating the quality of case-control studies involving the association between tobacco exposure and diseases in a Chinese population based on the Newcastle-Ottawa scale and post-hoc power. Biomed Environ Sci 2022; 35(9):861-6.
  21. Torabi R, Karampour MO, Mohammadzadeh A, Arefi S, Keramatipour M, Zarei S, et al. The relationship between polymorphisms of blood coagulation factor V gene and recurrent pregnancy losses. Journal of Reproduction & Infertility 2009; 9(4).
  22. Aarabi M, Memariani T, Arefi S, Aarabi M, Hantoosh Zadeh S, Akhondi MA, et al. Polymorphisms of plasminogen activator inhibitor-1, angiotensin converting enzyme and coagulation factor XIII genes in patients with recurrent spontaneous abortion. The Journal of Maternal-Fetal & Neonatal Medicine 2011; 24(3):545-8.
  23. Bagheri M, Rad IA, Nanbakhsh F. Factor V Leiden G1691A and factor II G20210A point mutations and pregnancy in North-West of Iran. Archives of gynecology and obstetrics 2011; 284(5):1311-5.
  24. Parand A, Zolghadri J, Nezam M, Afrasiabi A, Haghpanah S, Karimi M. Inherited thrombophilia and recurrent pregnancy loss. Iranian Red Crescent medical journal 2013; 15(12):e13708.
  25. Eskandari F, Akbari MT, Karizi SZ. Association of C677T and A1298C polymorphisms of the MTHFR gene with recurrent pregnancy loss. Pajoohande 2013; 18(4):167-73.
  26. Poursadegh Zonouzi A, Chaparzadeh N, Ghorbian S, Sadaghiani MM, Farzadi L, Ghasemzadeh A, et al. The association between thrombophilic gene mutations and recurrent pregnancy loss. Journal of assisted reproduction and genetics 2013; 30(10):1353-9.
  27. Khosravi F, Zarei S, Ahmadvand N, Akbarzadeh-Pasha Z, Savadi E, Zarnani AH, et al. Association between plasminogen activator inhibitor 1 gene mutation and different subgroups of recurrent miscarriage and implantation failure. Journal of assisted reproduction and genetics 2014; 31(1):121-4.
  28. Eskandari F, Zare Karizi SH, Akbari MT. Investigation of the association between polymorphisms of factor V (G1691A) and factor II (G20210A) with recurrent miscarriage in Iranian patients. Arak Univ J 2015; 18:1-9.
  29. Farahmand K, Totonchi M, Hashemi M, Reyhani Sabet F, Kalantari H, Gourabi H, et al. Thrombophilic genes alterations as risk factor for recurrent pregnancy loss. The Journal of Maternal-Fetal & Neonatal Medicine 2016; 29(8):1269-73.
  30. Besharat M, Tabandeh A, Keshtkar A, Mobasheri E, Besharat S, Joshaghani H. Evaluation of some plasma coagulation factors in women with spontaneous miscarriage. International Journal of Fertility & Sterility 2015; 9(3):309.
  31. Najafian M, Ahmadi EY, Asl JM, Shariati G, Ahmadi NY. Study the correlation between polymorphism of MTHFR thrombophilic genes and pregnancy loss in Ahvaz city. Biosciences biotechnology research asia 2016; 13(2):681-6.
  32. Sajjadi SM, Khosravi A, Pakravesh J, Soheili ZS, Samiei S, Mohammadi S, et al. Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study. Frontiers in Biology 2016; 11(6):471-5.
  33. Isazadeh A, Haj Azimian S, Tariverdi N, Rahmani SA, Esmaeili M, Karimkhanilouei S, et al. Effects of coagulation factor XIII (Val34Leu) polymorphism on recurrent pregnancy loss in Iranian Azeri women. LaboratoriumsMedizin 2017; 41(2):89-92.
  34. Isazadeh A, Hajazimian S, Rahmani SA, Mohammadoo-Khorasani M, Samanmanesh S, Karimkhanilouei S. The effects of Factor II (rs1799963) polymorphism on recurrent pregnancy loss in Iranian Azeri women. La Rivista Italiana della Medicina di Laboratorio-Italian Journal of Laboratory Medicine 2017; 13(1):37-40.
  35. Bigdeli R, Younesi MR, Panahnejad E, Asgary V, Heidarzadeh S, Mazaheri H, et al. Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population. Systems biology in reproductive medicine 2018; 64(4):274-82.
  36. Kardi MT, Yousefian E, Allahveisi A, Alaee S. Association of factor V Leiden and prothrombin G20210A polymorphisms in women with recurrent pregnancy loss in Isfahan province, Iran. International journal of preventive medicine 2018; 9(1):13.
  37. Zarfeshan Fard Y, Kooshkaki O, Kordi Tammandani D, Anani Sarab G. Investigation of the association between C677T polymorphism of the MTHFR gene and plasma homocysteine level in recurrent fetal miscarriage. Journal of Obstetrics and Gynaecology Research 2019; 45(8):1442-7.
  38. Ahangari N, Doosti M, Mousavifar N, Attaran M, Shahrokhzadeh S, Memarpour S, et al. Hereditary thrombophilia genetic variants in recurrent pregnancy loss. Archives of gynecology and obstetrics 2019; 300(3):777-82.
  39. Houjaghani S, Ghorbani A. The association of factor V Leiden mutation (G1691A) with pregnancy complications (miscarriage) in the Iran, East Azerbaijan. Clinical and Experimental Health Sciences 2022; 12(2):315-22.
  40. Ghaderi Nejad N, Saboori F, Mansour Samaei N, Kordi-Tamandani DM. The relationship between FXIII Val34Leu and PAI-1 4G/5G gene polymorphisms and recurrent miscarriage in women from Golestan province. Journal of Epigenetics 2022; 3(1):7-12.
  41. Moqadami A, Rezaei A, Ahmadi A, Badamchizadeh P, Karimi Z, Molaei F, et al. Investigating the association of MTHFR C677T gene polymorphism with recurrent spontaneous abortion among Azerbaijani women from northwest Iran. Genetic Testing and Molecular Biomarkers 2023; 27(10):339-44.
  42. Javan MR, Moghimian-Boroujeni B, Ayatollahi H, Ayatollahi A, Amini N, Jafaei E, et al. The Role of Thrombophilia Factors Polymorphism and Cytogenetic Analysis in Recurrent Pregnancy Loss (RPL) in Northeastern Iran. Journal of Obstetrics, Gynecology and Cancer Research 2023; 8(4):342-9.
  43. Ameri A, Khashei Varnamkhasti K, Parhoudeh S, Khashei Varnamkhasti S, Naeimi L, Naeimi S. Spontaneous miscarriage driven by maternal genetic mutation at position of PAI-1-844G/A: shed light on a race-specific genetic polymorphism. BMC Research Notes 2023; 16(1):360.
  44. Shang X, Luo Z, Li X, Hu F, Zhao Q, Zhang W. Meta‑analysis of Factor V Leiden G1691A polymorphism and osteonecrosis of femoral head susceptibility. Biomedical reports 2013; 1(4):594-8.
  45. Li C, Ren H, Chen H, Song J, Li S, Lee C, et al. Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk in an age-related manner: A systematic review and meta-analysis. Scientific reports 2017; 7(1):13550.
  46. González-Conejero R, Fernández-Cadenas I, Iniesta JA, Marti-Fabregas J, Obach V, Alvarez-Sabín J, et al. Role of fibrinogen levels and factor XIII V34L polymorphism in thrombolytic therapy in stroke patients. Stroke 2006; 37(9):2288-93.
  47. Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. European journal of medical genetics 2015; 58(1):1-10.
  48. Dong X, Wang J, Wang G, Wang J, Wang L, Du Y. MTHFR A1298C gene polymorphism on stroke risk: an updated meta-analysis. Genes and Environment 2021; 43(1):40.
  49. Maghsudlu M, Noroozi Z, Zokaei E, Motevaseli E. Systematic review and meta-analysis of association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss: an update. Thrombosis Journal 2024; 22(1):44.
  50. Eshre Guideline Group on RPL, Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, et al. ESHRE guideline: recurrent pregnancy loss. Human reproduction open 2018; 2018(2):hoy004.
  51. Esmaeilzadeh S, Jazayeri O, Aghajani MM, Amiri SS, GolsorkhtabarAmiri M, Delavar MA, et al. Paternal thrombophilia and recurrent implantation failure: an exploratory case-control study. JBRA Assisted Reproduction 2024; 28(3):435.
  52. Sayal HB, Beksac MS. The effect of hereditary thrombophilia on recurrent pregnancy loss: a retrospective cohort study. BMC Pregnancy and Childbirth 2024; 24(1):719.
  53. Eslami MM, Khalili M, Soufizomorrod M, Abroun S, Razi B. Factor V Leiden 1691G> A mutation and the risk of recurrent pregnancy loss (RPL): systematic review and meta-analysis. Thrombosis Journal 2020; 18(1):11.
  54. Liu X, Chen Y, Ye C, Xing D, Wu R, Li F, et al. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Human Reproduction 2021; 36(5):1213-29.
  55. Abbaszadeh E, Rahmani SA, Danaei Mehrabad S. Prevalence of mutations in V Leiden and prothrombin genes in women with recurrent pregnancy loss: A retrospective study on Iranian Azeri women. Journal of Basic Research in Medical Sciences 2020; 7(1):22-7.
  56. Rezanezhadi M, Joshagani HR. Relationship between Coagulation Factors and Polymorphism of Effective Thrombophilic Genes with Recurrent Abortions. Journal of Gorgan University of Medical Sciences 2022; 24(4):111-7.
  57. Zolfaghari M, Tavallaei M, Hosseini SM. Association between thrombophilic gene polymorphisms and recurrent pregnancy loss in Iranian Women. Archives of Pharmacy Practice 2020; 11(4-2020):184-8.
  58. Yengel I, Yorulmaz T, Api M. Association between FVL G1691A, FII G20210A, and MTHFR C677T and A1298C polymorphisms and Turkish women with recurrent pregnancy loss. Medicinski Glasnik 2019; 17(1):129-35.
  59. Gao H, Tao FB. Prothrombin G20210A mutation is associated with recurrent pregnancy loss: a systematic review and meta-analysis update. Thrombosis research 2015; 135(2):339-46.
  60. Wu X, Zhao L, Zhu H, He D, Tang W, Luo Y. Association between the MTHFR C677T polymorphism and recurrent pregnancy loss: a meta-analysis. Genetic testing and molecular biomarkers 2012; 16(7):806-11.
  61. Alfaleh A, Alkattan A, Mahmoud N, Alfaleh F, Almutair N, Alanazi A, et al. The association between MTHFR C677T gene polymorphism and repeated pregnancy loss in arabic countries: a systematic review and meta-analysis. Reproductive Sciences 2023; 30(7):2060-8.
مجله زنان، مامایی و نازایی ایران
دوره 28، شماره 12
اسفند 1404
صفحه 66-91

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