HLA-G rs1632947 AA Genotype as a Predictive Biomarker for IVF Failure: A Case-Control Study in Iraqi Women
Keywords:
HLA-G, rs1632947, IVF failure, genetic polymorphismAbstract
Background: Human leukocyte antigen-G (HLA-G) plays a critical role in immune tolerance during pregnancy, and its genetic polymorphisms have been linked to reproductive disorders. This study aimed to investigate the association between HLA-G polymorphisms (rs1632947) and in vitro fertilization (IVF) outcomes in Iraqi women.
Methods: A case-control study was conducted involving 30 women with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL) and 30 fertile controls. Genotyping was performed using PCR-RFLP, HLA-G mRNA expression was quantified via qRT-PCR, and plasma soluble HLA-G (sHLA-G) levels were measured by ELISA. Statistical analyses included chi-square tests, Student’s t-tests, and odds ratios (ORs).
Results: The rs1632947 AA genotype was significantly more frequent in infertile women (41%) compared to controls (10%) (OR = 13.75, p = 0.0178), with the A allele associated with increased risk (OR = 3.967, p = 0.0115). HLA-G expression was upregulated in infertile women (1.95-fold, p = 0.0442), particularly in GA heterozygotes (2.68-fold). Lower sHLA-G levels were observed in infertility cases, suggesting impaired immune tolerance.
Conclusion: The HLA-G rs1632947 AA genotype is a potential genetic marker for IVF failure, likely mediated through immune dysregulation. These findings support integrating HLA-G genotyping into IVF risk stratification and highlight avenues for immunotherapy-based interventions.
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S. Leslie, T. Soon-Sutton, and M. A. B. Khan, “Male infertility,” StatPearls, 2024.
S. Abdoli, S. Z. Masoumi, and F. Kazemi, “Environmental and occupational factors and higher risk of couple infertility: A systematic review study,” Middle East Fertil. Soc. J., vol. 27, no. 1, p. 33, 2022.
E. Somigliana, P. Vigano, A. Busnelli, A. Paffoni, W. Vegetti, and P. Vercellini, “Repeated implantation failure at the crossroad between statistics, clinics and over-diagnosis,” Reprod. Biomed. Online, vol. 36, no. 1, pp. 32–38, 2018.
P. Amini, F. Ramezanali, M. Parchehbaf-Kashani, S. Maroufizadeh, R. Omani-Samani, and A. Ghaheri, “Factors associated with in vitro fertilization live birth outcome: A comparison of different classification methods,” Int. J. Fertil. Steril., vol. 15, no. 2, p. 128, 2021.
H. Chen et al., “Impact of body mass index (BMI) on the success rate of fresh embryo transfer in women undergoing first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment,” Int. J. Obes., vol. 46, no. 1, pp. 202–210, 2022.
L. Boucret et al., “Endometriosis lowers the cumulative live birth rates in IVF by decreasing the number of embryos but not their quality,” J. Clin. Med., vol. 9, no. 8, p. 2478, 2020.
F. Sabbatino et al., “Role of human leukocyte antigen system as a predictive biomarker for checkpoint-based immunotherapy in cancer patients,” Int. J. Mol. Sci., vol. 21, no. 19, p. 7295, 2020.
Z. Djaoud and P. Parham, “HLAs, TCRs, and KIRs, a triumvirate of human cell-mediated immunity,” Annu. Rev. Biochem., vol. 89, pp. 717–739, 2020.
O. A. G. Tantengco et al., “Histocompatibility antigen, class I, G (HLA-G)’s role during pregnancy and parturition: a systematic review of the literature,” Life, vol. 11, no. 10, p. 1061, 2021.
H. Khani, M. A. H. Feizi, R. Safaralizadeh, J. Mohseni, and M. Haghi, “Altered Expression of the HLA-G and IL10RB Genes in Placental Tissue of Women with Recurrent Pregnancy Loss.,” Clin. Lab., vol. 69, no. 5, 2023.
B. Zhuang, J. Shang, and Y. Yao, “HLA-G: An important mediator of maternal-fetal immune-tolerance,” Front. Immunol., vol. 12, p. 744324, 2021.
L. Liu, L. Wang, L. Zhao, C. He, and G. Wang, “The role of HLA-G in tumor escape: manipulating the phenotype and function of immune cells,” Front. Oncol., vol. 10, p. 597468, 2020.
N. I. Ismail, “Relative expression of receptors in uterine natural killer cells compared to peripheral blood natural killer cells,” Front. Immunol., vol. 14, p. 1166451, 2023.
Z. Albayati et al., “The Influence of Cytomegalovirus on Expression of HLA‐G and its Ligand KIR 2 DL 4 by Human Peripheral Blood Leucocyte Subsets,” Scand. J. Immunol., vol. 86, no. 5, pp. 396–407, 2017.
W. He, “Investigation of HLA-E intracellular transport and antigen presentation.” University of Oxford, 2023.
G. Amodio and S. Gregori, “HLA-G genotype/expression/disease association studies: success, hurdles, and perspectives,” Front. Immunol., vol. 11, p. 549801, 2020.
G. Zheng, L. Jia, and A.-G. Yang, “Roles of HLA-G/KIR2DL4 in breast cancer immune microenvironment,” Front. Immunol., vol. 13, p. 791975, 2022.
X. Xu, Y. Zhou, and H. Wei, “Roles of HLA-G in the maternal-fetal immune microenvironment,” Front. Immunol., vol. 11, p. 592010, 2020.
A. Verloes et al., “The role of methylation, DNA polymorphisms and microRNAs on HLA-G expression in human embryonic stem cells,” Stem Cell Res., vol. 19, pp. 118–127, 2017.
Castelli, E. C., De Almeida, B. S., Muniz, Y. C. N., Silva, N. S. B., Passos, M. R. S., Souza, A. S., Page, A. E., Dyble, M., Smith, D. & Aguileta, G. 2021. HLA-G genetic diversity and evolutive aspects in worldwide populations. Scientific reports, 11, 23070.
[Nowak, I., Wilczyńska, K., Radwan, P., Wiśniewski, A., Krasiński, R., Radwan, M., Wilczyński, J. R., Malinowski, A. & Kuśnierczyk, P. 2020. Association of Soluble HLA-G Plasma Level and HLA-G Genetic Polymorphism With Pregnancy Outcome of Patients Undergoing in vitro Fertilization Embryo Transfer. Frontiers in Immunology, 10.
Moqadami, A., Aslani, N. & Khalaj-Kondori, M. 2024. Association of rs1632944 and rs1632947 polymorphisms of the HLA-G gene promoter with recurrent spontaneous abortion among Azerbaijani women from northwest Iran. Iranian Journal of Neonatology.
Berger, D. S., Hogge, W. A., Barmada, M. M. & Ferrell, R. E. 2010. Comprehensive analysis of HLA-G: implications for recurrent spontaneous abortion. Reproductive sciences, 17, 331-338.
Aljumaili, K. M. H., Haghi, M., Khalaj Kondori, M., Ardalan, M. R. & Hosseinpour Feizi, M. A. 2025. Association Study of rs1632947, rs1233334, and rs371194629 Polymorphisms in Human Leukocyte Antigen G Gene Expression and soluble Human Leukocyte Antigen G with Lupus. DNA and Cell Biology, 44, 25-31.
Merdas, A. H., Iqbal, M. N. & Alyasiri, N. S. 2022. The Effects of HLA-G Gene Polymorphism and sHLA-G Level in Women with Threatened Abortion. Journal of Techniques, 4, 69-74.
Hu, L., He, D. & Zeng, H. 2022. Association of parental HLA-G polymorphisms with soluble HLA-G expressions and their roles on recurrent implantation failure: A systematic review and meta-analysis. Frontiers in Immunology, 13, 988370.
Costa, C. H., Gelmini, G. F., Wowk, P. F., Mattar, S. B., Vargas, R. G., Roxo, V. M., Schuffner, A. & Bicalho Mda, G. 2012. HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment. Hum Immunol, 73, 891-7.
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