Axis Journal of Medical and Biosocial Sciences (AJMBS)

PREVALENCE OF DNA REPAIR GENE POLYMORPHISMS IN YOUNG WOMEN WITH RECURRENT PREGNANCY LOSS

Authors

  • Ali Ghulam

    Author

  • Arbab Tahir Ali

    Author

Keywords:
Allele Frequency, DNA Repair, Genetic Polymorphism, Pregnancy Loss, Recurrent, Women, XRCC1 Protein
Abstract

Background: Recurrent pregnancy loss (RPL) is a distressing reproductive condition with multifactorial etiologies. While anatomical, endocrine, and immunological factors are well documented, genetic contributors, particularly polymorphisms in DNA repair genes, have received increasing attention. Defective DNA repair mechanisms may compromise embryonic genomic stability, predisposing to repeated pregnancy loss, especially among younger women in whom age-related chromosomal abnormalities are less influential.

Objective: To assess the prevalence of DNA repair gene polymorphisms in young women with recurrent pregnancy loss.

Methods: A cross-sectional study was conducted in Karachi over five months, enrolling 80 women aged 20–35 years with ≥2 consecutive miscarriages before 20 weeks of gestation. Participants with uterine malformations, endocrine disorders, systemic illness, or acquired thrombophilia were excluded. Genomic DNA was extracted from peripheral blood and analyzed for XRCC1 (Arg399Gln), XRCC3 (Thr241Met), and XPD (Lys751Gln) polymorphisms using PCR–RFLP. Descriptive statistics were applied to calculate genotype frequencies, while chi-square and ANOVA tests were used to compare clinical characteristics across genotypic groups.

Results: At least one DNA repair gene variant was detected in 73.8% of participants, with 26.3% carrying polymorphisms in more than one gene. XRCC1 heterozygous and homozygous mutant genotypes were observed in 45.0% and 17.5% respectively, while XRCC3 showed 40.0% heterozygous and 17.5% homozygous mutant distributions. XPD variants were present in 41.3% heterozygous and 12.5% homozygous mutants. Carriers of XRCC1 and XRCC3 mutant alleles demonstrated significantly higher miscarriage frequency (p<0.05) and earlier gestational loss compared to wild-type carriers.

Conclusion: A high prevalence of DNA repair gene polymorphisms was observed in young women with recurrent pregnancy loss, with XRCC1 and XRCC3 variants significantly associated with adverse reproductive outcomes. Broader multicenter studies are required to validate these findings and explore their potential role in genetic screening for RPL.

Keywords: Allele Frequency, DNA Repair, Genetic Polymorphism, Pregnancy Loss, Recurrent, Women, XRCC1 Protein

Author Biographies
  1. Ali Ghulam

    Assistant Professor, Information Technology Centre, Sindh Agriculture University, Tandojam, Pakistan.

  2. Arbab Tahir Ali

    PHD Scholar,  Department of Pharmacy, University of Peshawar, Pakistan.

References

1. Cheng Z, Cheng D, Li J, Guo L, Zhang W, Zhang C, et al. Polymorphisms within DNA double-strand breaks repair-related genes contribute to structural chromosome abnormality in recurrent pregnancy loss. 2021;12:787718.

2. Fu W, Cui Q, Bu Z, Shi H, Yang Q, Hu LJFiE. Elevated sperm DNA fragmentation is correlated with an increased chromosomal aneuploidy rate of miscarried conceptus in women of advanced age undergoing fresh embryo transfer cycle. 2024;15:1289763.

3. Ramadan RA, Desouky LM, Elnaggar MA, Moaaz M, Elsherif AMJGt, biomarkers m. Association of DNA repair genes XRCC1 (Arg399Gln),(Arg194Trp) and XRCC3 (Thr241Met) polymorphisms with the risk of breast cancer: a case–control study in Egypt. 2014;18(11):754-60.

4. Flach J. The effects of aging on hematopoietic stem cells. 2016.

5. Kali Z, Cagiran F, Kirici P, Dogan C, Celik OJERfM, Sciences P. DNA repair gene (XRCC1 and XPD) polymorphism and risk of primary ovarian failure. 2022;26(18).

6. Skjelbred CF, Svendsen M, Haugan V, Eek AK, Clausen KO, Svendsen MV, et al. Influence of DNA repair gene polymorphisms of hOGG1, XRCC1, XRCC3, ERCC2 and the folate metabolism gene MTHFR on chromosomal aberration frequencies. 2006;602(1-2):151-62.

7. Soliman AH, Zaki NN, Fathy HM, Mohamed AA, Ezzat MA, Rayan AJES, et al. Genetic polymorphisms in XRCC1, OGG1, and XRCC3 DNA repair genes and DNA damage in radiotherapy workers. 2020;27(35):43786-99.

8. Saadat I, Beyzaei Z, Aghaei F, Kamrani S, Saadat MJAog, obstetrics. Association between polymorphisms in DNA repair genes (XRCC1 and XRCC7) and risk of preeclampsia. 2012;286(6):1459-62.

9. Szatkowska M, Zdrada-Nowak JJC. Genetic Polymorphisms in Base Excision Repair (BER) and Nucleotide Excision Repair (NER) Pathways as Potential Biomarkers for Gynecological Cancers: A Comprehensive Literature Review. 2025;17(13):2170.

10. Felini MJ. Reproductive factors and hormonal use and DNA repair polymorphisms XRCC1 and MGMT and adult-onset gliomas: The University of North Carolina at Chapel Hill; 2006.

11. Mashkina EJOJoH, Sciences A. Cell Cycle Control Gene-Gene Interaction Model in Pregnancy Loss. 2016;14(4).

12. Wang J, Guan C, Sui J, Zang Y, Wu Y, Zhang R, et al. Association between polymorphisms rs2228001 and rs2228000 in XPC and genetic susceptibility to preeclampsia: a case control study. 2021;21(1):787.

13. Macías-Gómez NM, Peralta-Leal V, Meza-Espinoza JP, Gutiérrez-Angulo M, Durán-González J, Ramírez-González JM, et al. Polymorphisms of the XRCC1 gene and breast cancer risk in the Mexican population. 2015;14(3):349-54.

14. Gielecińska A, Kciuk M, Kołat D, Kruczkowska W, Kontek RJIJoMS. Polymorphisms of DNA repair genes in thyroid Cancer. 2024;25(11):5995.

15. Bassi CL, Xavier D, Palomino G, Nicolucci P, Soares C, Sakamoto-Hojo ET, et al. Efficiency of the DNA repair and polymorphisms of the XRCC1, XRCC3 and XRCC4 DNA repair genes in systemic lupus erythematosus. 2008;17(11):988-95.

16. Costa SMAd. DNA repair genetic polymorphisms and breast cancer in the Portuguese population. 2007.

17. Neri MG. The role of N-acetylcisteine and genetic polymorphisms in XRCC1, XRCC3, GST genes in the modulation of DNA damage and tissue toxicity induced by medical ionizing radiation exposure. 2013.

18. Guven M, Guven GS, Oz E, Ozaydin A, Batar B, Ulutin T, et al. DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency. 2007;22(6):355-60.

19. Ryk C. Influence of genetic polymorphisms on DNA repair, p53 mutations and cancer risk: Karolinska Institutet (Sweden); 2006.

20. Ruszczyk MU. Associations between DNA repair SNPs and outcomes to platinum-based chemotherapy in ovarian cancer patients: State University of New York at Buffalo; 2009.

21. Silva SN, Gomes BC, Gaspar JF, Rueff J. DNA repair perspectives in thyroid and breast cancer: the role of DNA repair polymorphisms: INTECH Open Access Publisher; 2011.

Cover Image
Axis Journal of Medical and Biosocial Sciences
Downloads
Published
2024-11-30
Issue
Vol. 1 No. 1 (2024): Axis Journal of Medical and Biosocial Sciences (AJMBS)
Section
Articles
License

Copyright (c) 2024 Muhammad Fahad Imtiaz, Farah Niaz Awan (Author)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

https://creativecommons.org/licenses/by/4.0/

How to Cite

PREVALENCE OF DNA REPAIR GENE POLYMORPHISMS IN YOUNG WOMEN WITH RECURRENT PREGNANCY LOSS. (2024). Axis Journal of Medical and Biosocial Sciences, 1(1), 65-77. https://axisjmbs.com/index.php/home/article/view/8