Integrin Alpha2 and Integrin Beta3 Polymorphisms are Risk Factors for Infertility in Iraqi Infertile Females under In vitro Fertilization Program

Authors

  • Asmaa M. Salih Almohaidi Biology Department, College of Science for Women, the University of Baghdad, Baghdad, Iraq.
  • Rabab A.Yousif Al-Manaqib Intermediate School for Girls, Ministry of Education, Baghdad, Iraq.

DOI:

https://doi.org/10.21123/bsj.2024.8217

Keywords:

HRM, RT-PCR, implantation, ITGA2 gene, ITGB3 Gene, IVF.

Abstract

The current study was designed to investigate the impact of the Single Nucleotide Polymorphism (SNP), rs5918 (T>C), of integrin beta 3 genes (ITGB3) and rs1801106 (G>A) of integrin alpha 2 genes ( ITGB3 ) in peripheral blood samples of Iraqi female; 71 infertile females under IVF protocol ( divided into two subgroups, 29 success implantation and 42 failure implantation) and   50 fertile females as control. From March 2021 to August 2021, blood samples were taken from the patients and control groups at Roh al-Hayat center in Baghdad, Iraq. The genotyping of SNPs was carried out by using high-resolution melting real-time polymerase chain reaction (HRM real-time PCR) of the purified genomic DNA obtained from blood samples. The findings demonstrated that fertile females had significantly greater levels of the TT and GG genotypes of rs5918 at ITGB3 and rs1801106 at ITGA2, respectively, than infertile females. that shows the GG genotype functions as a protective factor, while the TC genotype of rs5918 at ITGB3 and AA genotype of rs1801106 at ITGA2 act as risk factors. In conclusion, these SNPs in the ITGA2 and ITGB3 genes may have an influence on the predisposition of a certain group to infertility.

References

Sun Y, Zhang Y. Ma X, Jia W , Su Y. Determining diagnostic criteria of unexplained recurrent implantation failure: A retrospective study of the two vs three or more implantation failure. Front. Endocrinol. 2021; 12: 851. https://doi.org/10.3389/fendo.2021.619437.

Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018; 62: 2-10.‏ https://doi.org/10.1016/j.clinbiochem.2018.03.012 .

Akhondi M M, Ranjbar F, Shirzad M, Ardakani Z B, Kamali, K , Mohammad K. Practical difficulties in estimating the prevalence of primary infertility in Iran. Int J Fertil Steril. 2019; 13(2): 113.‏ https://doi.org/10.22074%2Fijfs.2019.5583.

World Health Organization. Infertility.: http//www.who.int /2021.

World Health Reorganization. Iraqi Family Health Survey report. http//www.who.int /2008.

Hassab, Z S. Almohaidi A M S. Alsaidi F S. Association between the Genetic Variation of LIF R Gene with Its Gene Expression and Implantation Outcomes of IVF-Iraqi Arab Females. J Pharm Negat Results. 2022; 13( 4). https://doi.org/ 10.47750/pnr.2022.13.04.230.

Thabit, M A. Abdullah G H. AL-Rawi K F. Polymorphism study of MTHFR 677C? T and its correlation with oxidative stress and their influence on female infertility in Erbil–Iraq. Baghdad Sci J. 2017; 14(3): 0611-0611.‏ http://dx.doi.org/10.21123/bsj.2017.14.3.0611.

Centers for Disease Control and Prevention. Infertility FAQs. (2013). https://www.cdc.gov/reproductivehealth/infertility/index.htm.

Mitri F, Nayot D, Casper R F, Bentov Y. Current tools for the optimization of embryo transfer technique for recurrent implantation failure. Minerva Ginecol, 2016; 68(4): 431-449.

Ochoa-Bernal M A, Fazleabas A T . Physiologic events of embryo implantation and decidualization in human and non-human primates. Int. J Mol Sci. 2020; 21(6): 1973.‏ https://doi.org/10.3390/ijms21061973.

Raheem K A. Cytokines, growth factors and macromolecules as mediators of implantation in mammalian species. Int J Vet Sci Med. 2018; 6: S6-S14.

Jain M , Chauhan AK. Role of integrins in modulating smooth muscle cell plasticity and vascular remodeling: from expression to therapeutic implications. Cells. 2022; 11(4): 646. https://doi.org/10.3390/cells11040646

Mezu-Ndubuisi O J, Maheshwari A. The role of integrins in inflammation and angiogenesis. Pediatr Res. 2021; 89(7): 1619–1626. https://doi.org/10.1038/s41390-020-01177-9.

Busman H , Farisi S. Regulation of Integrin β3 Protein Secretion on Implantation Embryo of Mouse (Mus musculus L.) Induced by Oil Atsiri of Purple Nutsedge Tubers (Cyperus rotundus L.). Annu Res Rev Biol. 2019; 1-5.‏ https://doi.org/10.9734/arrb/2019/v33i230119

Zhou L , Li C, Liu X, Zhang T. Effect of Irisin on LIF and integrin αvβ3 in rats of implantation failure. Reprod Biol Endocrinol. 2021; 19(1): 1-7.‏ https://doi.org/10.1186/s12958-021-00700-9

Lessey B A. Endometrial integrins and the establishment of uterine receptivity. Hum. Reprod. 1998; 13: 247–258. https://doi.org/10.1093/humrep/13.suppl_3.247

Adorno-Cruz V, Liu H. Regulation and Functions of Integrin Alpha2 in Cell Adhesion and Disease. Genes Dis . 2019; 6(1): 16–24.https://doi.org/10.1016/j.gendis.2018.12.003

Simon M, Kouskouni E, Vitoratos N, Economou E, Creatsas G. Polymorphisms of platelet glycoprotein receptors and cell adhesion molecules in fetuses with fetal growth restriction and their mothers as detected with pyrosequencing. In Viv. 2017; 31: 243–50. https://doi.org/10.21873/invivo.11052

Al-Mishrey M K. Evaluation of Beta-2 Integrin and Platelets Roles in Sickle Cell Disease Pathogenicity in Basrah Governorate Patients. Baghdad Sci J. 2022; 20(1): 7-12 . http://dx.doi.org/10.21123/bsj.2022.6601.

Al-Qaisi R M, Al-Ani L , Al-Halbosiy M M. Genetic Polymorphism of ITGA2 Gene and the Risk of Heart Attack and Stroke in Al-Anbar Population/Iraq. J Pharm. Sci Res .2018; 10(9): 2305-2308.

Magazova A, Ashirbekov Y, Abaildayev A, Satken K, Balmukhanova A, Akanov Z, et al. ITGA2 Gene Polymorphism Is Associated with Type 2 Diabetes Mellitus in the Kazakhstan Population. Medicina, 2022; 58(10): 1416. https://doi.org/10.3390/medicina58101416

Database G H. ITGB3 Gene - GeneCards | ITB3 Protein | ITB3 Antibody. 2019.

Huang J, Li X, Shi X, Zhu M, Wang J, Huang S, Jin J. Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting. J hematol oncol. 2019; 12(26): 1-22.‏ https://doi.org/10.1186/s13045-019-0709-6.

Di Micco, P., Russo, V., Mastroiacovo, D., Bosevski, M., & Lodigiani, C. In vitro fertilization procedures with embryo transfer and their association with thrombophilia, thrombosis and early antithrombotic treatments. J. Blood Med. 2020 ; (11): 185-190.‏ https://doi.org/10.2147/JBM.S248988.

Yousif R A, Almohaidi A S , Al-Musawi B J. Assessment of ITGB3 gene expression and hormonal status in infertile female undergoing an in vitro fertilization protocol. HIV Nursing. 2023; 23(1): 770-778.‏ https://doi.org/10.31838/hiv23.01.130.

Yousif R A, Almohaidi A S. Identification of ITGB3 Polymorphisms with implantation outcome during in vitro fertilization program. HIV Nursing. 2023; 23(1): 257-264. https://doi.org/10.31838/hiv23.01.42.

Langsenlehner U, Renner W, Yazdani-Biuki B, Eder T , Wascher T C , Paulweber B. Integrin alpha-2 and beta-3 gene polymorphisms and breast cancer risk. Breast Cancer Res Treat. 2006; 97(1): 67-72.‏ https://doi.org/10.1007/s10549-005-9089-4

Newman P J, Derbes R S, Aster R H. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J clin invest. 1989; 83(5): 1778-1781.‏ https://doi.org/10.1172/JCI114082.

Buitrago L, Lefkowitz S, Bentur O, Padovan J, Coller B. Platelet binding to polymerizing fibrin is avidity driven and requires activated αIIbβ3 but not fibrin cross-linking. Blood Adv. 2021; 5(20):3986-4002.‏ https:// https://doi.org/10.1182/bloodadvances.2021005142.

Rotimi C, Leppert M, Matsuda I, Zeng C, Zhang H, Adebamowo C, et al. Community engagement and informed consent in the International HapMap project. Public Health Genom.2007 10(3): 186-198.‏ https://doi.org/10.1159/000101761.

Xiang Q, Ji SD, Zhang Z, Zhao X, Cui YM. Identification of ITGA2B and ITGB3 single-nucleotide polymorphisms and their influences on the platelet function. Biomed Res Int. 2016; 14 .https://doi.org/10.1155/2016/5675084

Komsa-Penkova R , Golemanov G, Tsankov B , Ivanov P , Beshev L , Tonchev P. Rs5918ITGB3 polymorphism, smoking, and BMI as risk factors for early onset and recurrence of DVT in young women. Clin Appl Thromb Hemost. 2017; 23(6): 585-595. https://doi.org/10.1177/1076029615624778

Oros M M, Lutz V, Pavlo A, Sitkar A. Investigation of the influence of thrombophilic genes polymorphism, including serpin 1 (pai-i), fii, prothrombin and ITGB3-β integrin, on the frequency of stroke in association with controllable risk factors for its occurrence. Wiad Lek. 2020; 73(3): 471-477.‏ https://doi.org/10.36740/WLek202003112

Yang W, Sun Q, Zhou Z, Gao Y, Shi F, Wu X, Kang, X. Coagulation parameters predictive of repeated implantation failure in Chinese women: A retrospective study. Medicine, . 2020; 99(48). https://doi.org/10.1097/MD.0000000000023320

.‏Karami F, Askari M, Modarressi M . Investigating association of rs5918 human platelets antigen 1 and rs1800790 fibrinogen β chain as critical players with recurrent pregnancy loss. Med Sci. 2018; 6(4): 98.‏ https://doi.org/10.3390/medsci6040098

Chatzidimitriou M, Chatzidimitriou D, Mavridou M, Anetakis C, Chatzopoulou F, Lialiaris T. Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women. Int J Lab Hematol. 2017; 39(6): 590-595.‏ https://doi.org/10.1111/ijlh.12703

Bigdeli R, Younesi M R, Panahnejad E, Asgary V, Heidarzadeh S, Mazaheri H, et al. Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population. Syst Biol Reprod Med. 2018; 64(4): 274-282.‏ https://doi.org/10.1080/19396368.2018.1456576

Al-Astal M, Sharif F. Beta-fibrinogen (-455 G/A) and Integrin beta-3 (PLA1/A2) polymorphisms and recurrent pregnancy loss in Gaza strip-Palestine. Int J Reprod Contracept Obstet Gynecol. 2014; 3(1): 134-139.‏ https://doi.org/10.1242/dev.162305.

Li Z, Li R, Li X, Dai H, Han X, Wang X, Yang A. LIF in embryo culture medium is a predictive marker for clinical pregnancy following IVF-ET of patients with fallopian tube obstruction. J Reprod Immunol. 2020; 141: 103164.‏ https://doi.10.1016/j.jri.2020.103164.

Kunicki T J, Williams S A, Diaz D, Farndale RW, Nugent D J. Platelet adhesion to decorin but not collagen I correlates with the integrin α2 dimorphism E534K, the basis of the human platelet alloantigen (HPA)-5 system. Haematologica. 2012; 97(5): 692.‏695. https://doi.org/10.3324%2Fhaematol.2011.056556

Kydonopoulou K, Rousso D, Ilonidis G, Mandala E. Association of GPIa C807T polymorphism with unexplained female infertility and IVF implantation failure. J Biol Regul Homeost Agents. 2019; 33(3): 883-887.‏

Lee C Q, Turco M Y, Gardner L, Simons B D, Hemberger M, Moffett A. Integrin α2 marks a niche of trophoblast progenitor cells in first trimester human placenta. Development. 2018; 145(16): dev162305.‏ https://doi.org/10.1242/dev.162305

Downloads

Issue

Section

article

How to Cite

1.
Integrin Alpha2 and Integrin Beta3 Polymorphisms are Risk Factors for Infertility in Iraqi Infertile Females under In vitro Fertilization Program. Baghdad Sci.J [Internet]. [cited 2024 Oct. 9];22(4). Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/8217