Single Nucleotide Pleomorphisms of Different Cytokines among Jordanian Patients with Lupus Nephritis: A Pilot Study
DOI:
https://doi.org/10.35516/jjps.v18i2.2833Keywords:
lupus nephritis, cytokines, SNPs, JordanAbstract
Lupus nephritis (LN) is one of the most common clinical manifestations of systemic lupus erythematosus (SLE) and significantly affects the morbidity and mortality associated with SLE. Both environmental and genetic factors contribute to the development of SLE. There is growing interest in identifying genetic markers, particularly cytokine-related variants, that may indicate susceptibility to SLE, predict future organ involvement, and monitor changes in disease activity. This study aims to examine a wide array of cytokine genetic variants and their association with LN in a cohort of 83 Jordanian samples. Genotyping was performed using the Polymerase Chain Reaction/Sequence Specific Primer (PCR/SSP) technique. Our results show an increased frequency of the G allele at the promoter region (-1082 A/G) of interleukin-10 (IL-10) in LN samples (p = 0.001) compared to controls, whereas the A allele predominated in the control group (p = 0.001). At the genotype level for the -1082 A/G promoter region of IL-10, the GG genotype was significantly associated with LN (p < 0.001), while the GA genotype predominated in controls (p = 0.027). No significant associations were observed between other cytokine SNPs (IFN-γ, IL-6, TNF-α) and LN in Jordanian SLE patients. Our pilot study suggests that the G allele and GG genotype at the IL-10 promoter region (-1082 A/G) increase the risk of developing LN in Jordanian SLE patients, while the A allele and GA genotype are more common in controls.
References
Su, D. L., Lu Z. M., Shen M. N., Li X. and Sun L. Y. Roles of pro- and anti-inflammatory cytokines in the pathogenesis of SLE. J Biomed Biotechnol. 2012; 2012: 347141. DOI: https://doi.org/10.1155/2012/347141
Goulielmos, G. N., Zervou M. I., Vazgiourakis V. M., Ghodke-Puranik Y., Garyfallos A. and Niewold T. B. The genetics and molecular pathogenesis of systemic lupus erythematosus (SLE) in populations of different ancestry. Gene. 2018; 668: 59-72. DOI: https://doi.org/10.1016/j.gene.2018.05.041
Talaat, R. M., Alrefaey S. A., Bassyouni I. H., Ashour M. E. and Raouf A. A. Genetic polymorphisms of interleukin 6 and interleukin 10 in Egyptian patients with systemic lupus eythematosus. Lupus. 2016; 25(3): 255-64. DOI: https://doi.org/10.1177/0961203315615219
Davis, L. S., Hutcheson J. and Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interferon Cytokine Res. 2011; 31(10): 781-9. DOI: https://doi.org/10.1089/jir.2011.0047
Alabbadi, Ibrahim, Massad Eman, Taani Nashaat, Dababneh Safwan, Shersheer Qasem, Nimri Omar, Mahmoud Refqi, Hijazeen Rami and Ishaq Adnan. Exploring the Economic Aspects of β-Thalassemia in Jordan in 2019. Jordan Journal of Pharmaceutical Sciences. 2022; 15(3): 390-404. DOI: https://doi.org/10.35516/jjps.v15i3.412
Alhawamdeh, Ebtesam, Bulatova Nailya R., Yousef Al Motassem F., AlAbbadi Mohammed A. and Omer Ethar A. A Cross-sectional Study of the Catalase Genetic Polymorphism (-262 cytosine/ thymine) and Blood Catalase Activity among Jordanian Vitiligo Patients. Jordan Journal of Pharmaceutical Sciences. 2023; 16(2): 330-344. DOI: https://doi.org/10.35516/jjps.v16i2.438
Nelson, P., Rylance P., Roden D., Trela M. and Tugnet N. Viruses as potential pathogenic agents in systemic lupus erythematosus. Lupus. 2014; 23(6): 596-605. DOI: https://doi.org/10.1177/0961203314531637
Buniello, A., MacArthur J. A. L., Cerezo M., Harris L. W., Hayhurst J., Malangone C., McMahon A., Morales J., Mountjoy E., Sollis E., Suveges D., Vrousgou O., Whetzel P. L., Amode R., Guillen J. A., Riat H. S., Trevanion S. J., Hall P., Junkins H., Flicek P., Burdett T., Hindorff L. A., Cunningham F. and Parkinson H. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 2019; 47(D1): D1005-d1012. DOI: https://doi.org/10.1093/nar/gky1120
Kwon, Y. C., Chun S., Kim K. and Mak A. Update on the Genetics of Systemic Lupus Erythematosus: Genome-Wide Association Studies and Beyond. Cells. 2019; 8(10). DOI: https://doi.org/10.3390/cells8101180
Chai, H. C., Phipps M. E. and Chua K. H. Genetic risk factors of systemic lupus erythematosus in the Malaysian population: a minireview. Clin Dev Immunol. 2012; 2012: 963730. DOI: https://doi.org/10.1155/2012/963730
Lewis, M. J. and Jawad A. S. The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus. Rheumatology (Oxford). 2017; 56(suppl_1): i67-i77.
Khdair, S. I., Al-Bdour R., Jarrar W., Hammad A., Al-Jayeh A., Masa'deh M., Adwan M. and Farah R. Immunogenetic Profiling of SLE and LN among Jordanian Patients. J Pers Med. 2022; 12(12). DOI: https://doi.org/10.3390/jpm12121955
López, P., Gutiérrez C. and Suárez A. IL-10 and TNFalpha genotypes in SLE. J Biomed Biotechnol. 2010; 2010: 838390. DOI: https://doi.org/10.1155/2010/838390
Liu, J., Liao M. Q., Cao D. F., Yang Y., Yang Y., Liu Y. H., Zeng F. F. and Chen X. H. The Association between Interleukin-6 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus: A Meta-analysis with Trial Sequential Analysis. Immunol Invest. 2021; 50(2-3): 259-272. DOI: https://doi.org/10.1080/08820139.2020.1769646
Song, G. G., Choi S. J., Ji J. D. and Lee Y. H. Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis. Hum Immunol. 2013; 74(3): 364-70. DOI: https://doi.org/10.1016/j.humimm.2012.11.020
Paradowska-Gorycka, A., Roszak M., Stypinska B., Lutkowska A., Walczyk M., Olesinska M., Wajda A., Piotrowski P., Puszczewicz M., Majewski D. and Jagodzinski P. P. IL-6 and TGF-β gene polymorphisms, their serum levels, as well as HLA profile, in patients with systemic lupus erythematosus. Clin Exp Rheumatol. 2019; 37(6): 963-975.
Umare, V. D., Pradhan V. D., Rajadhyaksha A. G., Patwardhan M. M., Ghosh K. and Nadkarni A. H. Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients. Hum Immunol. 2017; 78(2): 201-208. DOI: https://doi.org/10.1016/j.humimm.2016.11.002
Umare, V., Pradhan V., Dadheech S., Rajadhyaksha A., Ghosh K. and Nadkarni A. Cytokine genes multi-locus analysis reveals synergistic influence on genetic susceptibility in Indian SLE - A multifactor-dimensionality reduction approach. Cytokine. 2020; 135: 155240. DOI: https://doi.org/10.1016/j.cyto.2020.155240
Asano, N. M., Angelo H. D., da Silva H. A., Maia M. M., Lins O. G. and Souza P. E. Interleukin-6 promoter polymorphisms -174 G/C in Brazilian patients with systemic lupus erythematosus. Hum Immunol. 2013; 74(9): 1153-6. DOI: https://doi.org/10.1016/j.humimm.2013.05.015
Manolova, I., Miteva L., Ivanova M., Kundurzhiev T., Stoilov R. and Stanilova S. The Synergistic Effect of TNFA and IL10 Promoter Polymorphisms on Genetic Predisposition to Systemic Lupus Erythematosus. Genet Test Mol Biomarkers. 2018; 22(2): 135-140. DOI: https://doi.org/10.1089/gtmb.2017.0169
Yuan, Y., Wang X., Ren L., Kong Y., Bai J. and Yan Y. Associations between interleukin-10 gene polymorphisms and systemic lupus erythematosus risk: a meta-analysis with trial sequential analysis. Clin Exp Rheumatol. 2019; 37(2): 242-253.
Rosado, S., Rua-Figueroa I., Vargas J. A., Garcia-Laorden M. I., Losada-Fernandez I., Martin-Donaire T., Perez-Chacon G., Rodriguez-Gallego C., Naranjo-Hernandez A., Ojeda-Bruno S., Citores M. J. and Perez-Aciego P. Interleukin-10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands. Int J Immunogenet. 2008; 35(3): 235-42. DOI: https://doi.org/10.1111/j.1744-313X.2008.00762.x
Hee, Chee Seng, Gun Suk Chyn, Naidu Rakesh, Somnath Sushela Devi and Radhakrishnan Ammu Kutty %J International Journal of Rheumatic Diseases. The relationship between single nucleotide polymorphisms of the interleukin‐10 gene promoter in systemic lupus erythematosus patients in Malaysia: a pilot study. 2008; 11(2): 148-154. DOI: https://doi.org/10.1111/j.1756-185X.2008.00350.x
Lee, Y. H. and Bae S. C. Association between interferon-γ +874 T/A polymorphism and susceptibility to autoimmune diseases: a meta-analysis. Lupus. 2016; 25(7): 710-8. DOI: https://doi.org/10.1177/0961203315624557
Adwan, M. Clinical and Serologic Characteristics of Systemic Lupus Erythematosus in the Arab World: A Pooled Analysis of 3,273 Patients. Arch Rheumatol. 2018; 33(4): 455-463. DOI: https://doi.org/10.5606/ArchRheumatol.2018.6832
Bastian, H. M., Roseman J. M., McGwin G., Jr., Alarcón G. S., Friedman A. W., Fessler B. J., Baethge B. A. and Reveille J. D. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus. 2002; 11(3): 152-60. DOI: https://doi.org/10.1191/0961203302lu158oa
Webber, D., Cao J., Dominguez D., Gladman D. D., Levy D. M., Ng L., Paterson A. D., Touma Z., Urowitz M. B., Wither J. E., Silverman E. D. and Hiraki L. T. Association of systemic lupus erythematosus (SLE) genetic susceptibility loci with lupus nephritis in childhood-onset and adult-onset SLE. Rheumatology (Oxford). 2020; 59(1): 90-98. DOI: https://doi.org/10.1093/rheumatology/kez220
Aringer, M., Costenbader K., Daikh D., Brinks R., Mosca M., Ramsey-Goldman R., Smolen J. S., Wofsy D., Boumpas D. T., Kamen D. L., Jayne D., Cervera R., Costedoat-Chalumeau N., Diamond B., Gladman D. D., Hahn B., Hiepe F., Jacobsen S., Khanna D., Lerstrøm K., Massarotti E., McCune J., Ruiz-Irastorza G., Sanchez-Guerrero J., Schneider M., Urowitz M., Bertsias G., Hoyer B. F., Leuchten N., Tani C., Tedeschi S. K., Touma Z., Schmajuk G., Anic B., Assan F., Chan T. M., Clarke A. E., Crow M. K., Czirják L., Doria A., Graninger W., Halda-Kiss B., Hasni S., Izmirly P. M., Jung M., Kumánovics G., Mariette X., Padjen I., Pego-Reigosa J. M., Romero-Diaz J., Rúa-Figueroa Fernández Í, Seror R., Stummvoll G. H., Tanaka Y., Tektonidou M. G., Vasconcelos C., Vital E. M., Wallace D. J., Yavuz S., Meroni P. L., Fritzler M. J., Naden R., Dörner T. and Johnson S. R. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019; 78(9): 1151-1159. DOI: https://doi.org/10.1136/annrheumdis-2018-214819
Jarrar, Y. B. and Ghishan M. The Nudix Hydrolase 15 (NUDT15) Gene Variants among Jordanian Arab Population. Asian Pac J Cancer Prev. 2019; 20(3): 801-808. DOI: https://doi.org/10.31557/APJCP.2019.20.3.801
Al-Qerem, Walid, Safar Mohammad, Safar Ibrahim and Al-Ibadah Mahmood. Identifying factors associated with increased rate of mortality of COVID-19 patients among Jordanian population: A multicenter case-controlled retrospective study. Jordan Journal of Pharmaceutical Sciences. 2023; 16(2): 483. DOI: https://doi.org/10.35516/jjps.v16i2.1542
Ameer, M. A., Chaudhry H., Mushtaq J., Khan O. S., Babar M., Hashim T., Zeb S., Tariq M. A., Patlolla S. R., Ali J., Hashim S. N. and Hashim S. An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management. Cureus. 2022; 14(10): e30330. DOI: https://doi.org/10.7759/cureus.30330
Zhou, M., Ding L., Peng H., Wang B., Huang F., Xu W. D., Li J. H., Ye X. R., Pan H. F. and Ye D. Q. Association of the interleukin-10 gene polymorphism (-1082A/G) with systemic lupus erythematosus: a meta-analysis. Lupus. 2013; 22(2): 128-35. DOI: https://doi.org/10.1177/0961203312468623
Johanneson, B., Lima G., von Salomé J., Alarcón-Segovia D. and Alarcón-Riquelme M. E. A major susceptibility locus for systemic lupus erythemathosus maps to chromosome 1q31. Am J Hum Genet. 2002; 71(5): 1060-71. DOI: https://doi.org/10.1086/344289
Nath, S. K., Harley J. B. and Lee Y. H. Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet. 2005; 118(2): 225-34. DOI: https://doi.org/10.1007/s00439-005-0044-6
Rees, L. E., Wood N. A., Gillespie K. M., Lai K. N., Gaston K. and Mathieson P. W. The interleukin-10-1082 G/A polymorphism: allele frequency in different populations and functional significance. Cell Mol Life Sci. 2002; 59(3): 560-9. DOI: https://doi.org/10.1007/s00018-002-8448-0
Mohammadi, S., Saghaeian Jazi M., Zare Ebrahimabad M., Eghbalpour F., Abdolahi N., Tabarraei A. and Yazdani Y. Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population. Int J Immunogenet. 2019; 46(1): 20-30. DOI: https://doi.org/10.1111/iji.12407
da Silva, H. D., da Silva A. P., da Silva H. A., Asano N. M., Maia Mde M. and de Souza P. R. Interferon gamma and Interleukin 10 polymorphisms in Brazilian patients with systemic lupus erythematosus. Mol Biol Rep. 2014; 41(4): 2493-500. DOI: https://doi.org/10.1007/s11033-014-3106-9
Liu, P., Song J., Su H., Li L., Lu N., Yang R. and Peng Z. IL-10 gene polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis. PLoS One. 2013; 8(7): e69547. DOI: https://doi.org/10.1371/journal.pone.0069547
Ramírez-Bello, J., Cadena-Sandoval D., Mendoza-Rincón J. F., Barbosa-Cobos R. E., Sánchez-Muñoz F., Amezcua-Guerra L. M., Sierra-Martínez M. and Jiménez-Morales S. Tumor necrosis factor gene polymorphisms are associated with systemic lupus erythematosus susceptibility or lupus nephritis in Mexican patients. Immunol Res. 2018; 66(3): 348-354. DOI: https://doi.org/10.1007/s12026-018-8993-8
Tangwattanachuleeporn, M., Sodsai P., Avihingsanon Y., Wongpiyabovorn J., Wongchinsri J. and Hirankarn N. Association of interferon-gamma gene polymorphism (+874A) with arthritis manifestation in SLE. Clin Rheumatol. 2007; 26(11): 1921-4. DOI: https://doi.org/10.1007/s10067-007-0699-6







