Single nucleotide polymorphism of IL-18 (rs 1946519) in recurrent aborted Iraqi women and its association with toxoplasmosis
,
Abstract
The parasite Toxoplasma gondii infection causes toxoplasmosis. Although it is frequently asymptomatic, primary infection in pregnant women can result in serious and debilitating disease in the fetus. Increased knowledge of the significance of parasite genotype in determining infectivity and illness severity is among recent breakthrough. Interleukin 18 (IL-18) is an essential cytokine in immune response regulation and promotes Th1 and Th2 differentiation as well. This study aims to shed light on the risks of elevated levels of IL-18 in aborted women with toxoplasmosis through evaluate the risk or protective function of alleles or genotypes for single nucleotide polymorphism (SNP) of IL-18 (rs 1946519), which may be related to the susceptibility to toxoplasmosis. IL-18 levels in patient and control blood samples were determined using ELISA, and the SNP IL-18 (ra 1946519) was subjected to the high resolution method. The results showed that when compared to healthy pregnant women, the IL-18 serum levels of recurrent abortion with toxoplasmosis, recurrent abortion without toxoplasmosis, and healthy non-pregnant women decreased with significant differences. Additionally, a strong association between patients and controls was found in the SNP IL-18 data. Recurrent abortion women with toxoplasmosis and recurrent abortion women without toxoplasmosis with the genotypes AA and AC had significantly lower IL-18 serum levels than healthy pregnant women, according to the distribution of IL-18 serum levels by SNP. In conclusion, the serum level of IL-18 varied by genotype in patients with substantial differences compared to controls, while the SNP of IL-18 has been linked as a risk factor in toxoplasmosis-infected recurrent abortion women.
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Systematic Review and Meta-Analysis. Fetal Pediatr Pathol. 2020; 39(4):346-359.
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22. Ostojic S, Volk M, Medica I, et al. Polymorphisms in the interleukin-12/18 genes and recurrent spontaneous abortion. Am J Reprod Immunol. 2007; 58(5): 403- 408.
23. Basu M, Das T, Ghosh A, et al. Gene-Gene Interaction and Functional Impact of Polymorphisms on Innate Immune Genes in Controlling Plasmodium falciparum Blood Infection Level. PLoS One. 2012;7(10): e46441.
24. Semagn K, Babu R, Hearne S, Olsen M. Single nucleotide polymorphism genotyping using Kompetitive Allele Specific PCR (KASP): overview of the technology and its application in crop improvement. Molecular Breeding. 2013; 33(1):1–14.
25. Robert F, Pelletier J. Exploring the Impact of Single-Nucleotide Polymorphism on Translation. Front Genet. 2018; 9:507.
26. Baqer NN, Saheb EJ, Ahmed NS. Genetic polymorphism of IL-17A (rs2275913) in Iraqi women with recurrent abortion and its relationship with susceptibility to toxoplasmosis. Meta Gene. 2021; 29: 100939.
27. Baqer NN, Saheb EJ, Ahmed NS, Alhadad NA. The association of IL-3, IL-17A, and IL 27 serum levels with susceptibility to toxoplasmosis in recurrent abortion of Iraqi women. Exp Parasitol. 2022; 234: 108217.
28. Baqer NN, Ahmed NS, Saheb EJ. The association between serum level and genetic variation of IL-3 (rs40401) in recurrent abortion women infected with toxoplasmosis in Iraq. Cytokine. 2022; 149: 155718.
29. Passos ST, Silver JS, O,Hara AC, et al. IL- 6 promotes NK cell production of IL-17 during toxoplasmosis. J Immunol. 2010;184(4):1776-83.
30. Mohammed KG, EL-Shammary BA, Al- Jobouri SA, Al-Saheer HA. The role T- helper-17 in toxoplasmosis among women with abortion. Kufa Med J. 2012; 15(1):239- 244.
31. Silva JL, Rezende-Oliveira K, da Silva MV, et al. IL-17-expressing CD4⁺ and CD8⁺ T lymphocytes in human toxoplasmosis. Mediators Inflamm. 2014; 2014:573825.
32. El Shahaway AA, Abd Elhady RR, et al. Role of maternal serum interleukin 17 in preeclampsia: diagnosis and prognosis. J Inflamm Res. 2019; 12:175-180.
33. Gorfu G, Cirelli KM, Melo MB, et al. Dual Role for Inflammasome Sensors NLRP1 and NLRP3 in Murine Resistance to Toxoplasma gondii. mBio, 2014; 5(1): e01117- 13.
34. Gavrilescu LC, Denkers EY. IFN-gamma overproduction and high-level apoptosis are associated with high but not low virulence Toxoplasma gondii infection. J Immunol. 2001; 167(2):902-9.
35. Bayram DM, Hassan GM, Ali HZ. Detection of some CC Chemokine Ligands in Patients with Cutaneous Leishmaniasis. Iraqi J Sci. 2022; 63(4):431–1437.
36. Hassan GM, Ali HZ, Watheq MH. Evaluation of IL-8, nitric oxide and macrophage inhibitory factor as clinical circulatory markers in patients with cutaneous leishmaniasis, before and during sodium stibogluconate treatment. Cytokine. 2024; 173:156450.
2. Rossi M, Sharkey AM, Viganò P, et al. Identification of genes regulated by interleukin-1β in human endometrial stromal cells. Reproduction.2005; 130(5):721–9.
3. Meka A and Reddy BM. Recurrent Spontaneous Abortions: An Overview of Genetic and Non-Genetic Backgrounds. Int J Hum Genet. 2006; 6(2):109–17.
4. Calderwood C. Thromboembolism and thrombophilia in pregnancy. Curr Obstet Gynaecol. 2006: 16(6):321-326.
5. Wong LF, Porter TF, Scott JR. Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev. 2014; 2014(10):CD000112.
6. Chaouat G, Zourbas S, Ostojić S, et al. A brief review of recent data on some cytokine expressions at the materno-foetal interface, which might challenge the classical Th1/Th2 dichotomy. J Reprod Immunol. 2002; 53(1-2):241–56.
7. Costeas PA, Koumouli A, Giantsiou- Kyriakou A, Papaloizou A, Koumas L. Th2/Th3 cytokine genotypes are associated with pregnancy loss. Hum Immunol. 2004; 1; 65(2):135–41.
8. Jamieson SE, de Roubaix LA, Cortina-Borja M, et al. Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis. PLoS One. 2008; 3(6): e2285.
9. Saini V, Arora S, Yadav A, Bhattacharjee J. Cytokines in recurrent pregnancy loss. Clin Chim Acta. 2011; 412(9-10):702–8.
10. Justina D, Matos L, Medeiros MD, et al. Absence of interleukin-18 gene polymorph- isms and rheumatoid arthritis. Revista Iran J Parasitol: Vol. 19, No. 4, Oct-Dec 2024, pp.408-417 416 Available at: http://ijpa.tums.ac.ir Brasileira de Reumatologia. 2013; 53(2):199-
205.
11. Sugiura T, Maeno N, Kawaguchi Y, et al. A promoter haplotype of the interleukin-18 gene is associated with juvenile idiopathic arthritis in the Japanese population. Arthritis Res Ther.2006; 8(3):R60.
12. Srivastava S, Salim N, Robertson MJ. Interleukin-18: biology and role in the immunotherapy of cancer. Curr Med Chem. 2010; 17(29):3353-7.
13. Roland L, Gagné A, Bélanger MC, Boutet M, Julien P, Bilodeau JF. Plasma interleukin-18 (IL-18) levels are correlated with antioxidant vitamin coenzyme Q (10) in preeclampsia. Acta Obstet Gynecol Scand. 2010; 89(3):360-6.
14. Szarka A, Rigó J Jr, Lázár L, Beko G, Molvarec A. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol. 2010; 11:59.
15. Daskalakis G, Thomakos N, Papapanagio- tou A, Papantoniou N, Mesogitis S, Antsaklis A. Amniotic fluid interleukin-18 at mid-trimester genetic amniocentesis:
relationship to intraamniotic microbial invasion and preterm delivery. BJOG. 2009; 116(13):1743-8.
16. Lédée-Bataille N, Dubanchet S, Coulomb- L’hermine A, DurandGasselin I, Frydman R,
Chaouat G.A new role for natural killer cells, interleukin (IL)-12, and IL-18 in repeated implantation failure after in vitro fertilization. Fertil Steril. 2004; 81(1):59-65.
17. Laird SM, Tuckerman EM and Li TC. Cytokine expression in the endometrium of women with implantation failure and recurrent miscarriage. Reprod Biomed Online. 2006; 13(1):13-23.
18. Fehrmann RS, Jansen RC, Veldink JH, et al. Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet. 2011; 7(8):e1002197.
19. Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M. Mapping complex disease traits with global gene expression. Nat Rev Genet.2009; 10(3):184-94.
20. Salimi E, Karimi-Zarchi M, Dastgheib S, et al. Association of Promoter Region Polymorphisms of IL-6 and IL-18 Geneswith Risk of Recurrent Pregnancy Loss: A
Systematic Review and Meta-Analysis. Fetal Pediatr Pathol. 2020; 39(4):346-359.
21. Soheilyfar S, Nikyar T, Maroufi NF, et al. Association of IL-10, IL-18, and IL-33 genetic polymorphisms with recurrent pregnancy loss risk in Iranian women. Gynecol Endocrinol. 2019;35(4):342-345
22. Ostojic S, Volk M, Medica I, et al. Polymorphisms in the interleukin-12/18 genes and recurrent spontaneous abortion. Am J Reprod Immunol. 2007; 58(5): 403- 408.
23. Basu M, Das T, Ghosh A, et al. Gene-Gene Interaction and Functional Impact of Polymorphisms on Innate Immune Genes in Controlling Plasmodium falciparum Blood Infection Level. PLoS One. 2012;7(10): e46441.
24. Semagn K, Babu R, Hearne S, Olsen M. Single nucleotide polymorphism genotyping using Kompetitive Allele Specific PCR (KASP): overview of the technology and its application in crop improvement. Molecular Breeding. 2013; 33(1):1–14.
25. Robert F, Pelletier J. Exploring the Impact of Single-Nucleotide Polymorphism on Translation. Front Genet. 2018; 9:507.
26. Baqer NN, Saheb EJ, Ahmed NS. Genetic polymorphism of IL-17A (rs2275913) in Iraqi women with recurrent abortion and its relationship with susceptibility to toxoplasmosis. Meta Gene. 2021; 29: 100939.
27. Baqer NN, Saheb EJ, Ahmed NS, Alhadad NA. The association of IL-3, IL-17A, and IL 27 serum levels with susceptibility to toxoplasmosis in recurrent abortion of Iraqi women. Exp Parasitol. 2022; 234: 108217.
28. Baqer NN, Ahmed NS, Saheb EJ. The association between serum level and genetic variation of IL-3 (rs40401) in recurrent abortion women infected with toxoplasmosis in Iraq. Cytokine. 2022; 149: 155718.
29. Passos ST, Silver JS, O,Hara AC, et al. IL- 6 promotes NK cell production of IL-17 during toxoplasmosis. J Immunol. 2010;184(4):1776-83.
30. Mohammed KG, EL-Shammary BA, Al- Jobouri SA, Al-Saheer HA. The role T- helper-17 in toxoplasmosis among women with abortion. Kufa Med J. 2012; 15(1):239- 244.
31. Silva JL, Rezende-Oliveira K, da Silva MV, et al. IL-17-expressing CD4⁺ and CD8⁺ T lymphocytes in human toxoplasmosis. Mediators Inflamm. 2014; 2014:573825.
32. El Shahaway AA, Abd Elhady RR, et al. Role of maternal serum interleukin 17 in preeclampsia: diagnosis and prognosis. J Inflamm Res. 2019; 12:175-180.
33. Gorfu G, Cirelli KM, Melo MB, et al. Dual Role for Inflammasome Sensors NLRP1 and NLRP3 in Murine Resistance to Toxoplasma gondii. mBio, 2014; 5(1): e01117- 13.
34. Gavrilescu LC, Denkers EY. IFN-gamma overproduction and high-level apoptosis are associated with high but not low virulence Toxoplasma gondii infection. J Immunol. 2001; 167(2):902-9.
35. Bayram DM, Hassan GM, Ali HZ. Detection of some CC Chemokine Ligands in Patients with Cutaneous Leishmaniasis. Iraqi J Sci. 2022; 63(4):431–1437.
36. Hassan GM, Ali HZ, Watheq MH. Evaluation of IL-8, nitric oxide and macrophage inhibitory factor as clinical circulatory markers in patients with cutaneous leishmaniasis, before and during sodium stibogluconate treatment. Cytokine. 2024; 173:156450.
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| Issue | Vol 19 No 4 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v19i4.17161 | |
| Keywords | ||
| Toxoplasmosis Recurrent abortion IL-18 (rs 1946519) Single nucleotide polymorphism. | ||
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How to Cite
1.
Hadi Fadhil S, Jabbar Saheb E. Single nucleotide polymorphism of IL-18 (rs 1946519) in recurrent aborted Iraqi women and its association with toxoplasmosis. Iran J Parasitol. 2024;19(4):408-417.
