Association of Interleukin-2 Gene Polymorphism with Henoch-schönlein Purpura Nephritis
-
Jiajia Cao
,
Junfeng Zhang
,
Hui Xu
,
Wei Li
,
Jianrong Shi
,
Qing Ye
Abstract
Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis that mostly affects children, and previous studies have indicated that genetic factors may influence disease susceptibility. The aim of this study was to evaluate a possible association of three interleukin-2 (IL-2) gene polymorphisms (rs3136534, rs2069776, and rs2069762) with HSPN in the Chinese population.
A total of 81 patients with HSPN and 200 healthy children were enrolled. The distribution of genotypes, allelic frequencies, and haplotype frequencies among the three IL-2 polymorphisms were analyzed using the Sequenom MassARRAY system by means of matrix-assisted laser desorption ionization-time of flight mass spectrometry method.
Compared to the healthy controls, genotyping analysis demonstrated rs3136534 was associated with a decreased HSPN risk in the dominant inheritance model (G/T+T/T vs. G/G; OR, 0.54; 95% CI, 0.31–0.93). However, the frequency of the T allele and haplotypes of rs3136534 showed no statistical significance. For the frequency of genotype, allele, and haplotype of the rs2069776 and rs20697622 polymorphisms, no significant differences were observed between HSPN patients and controls.
Our results suggest that the rs3136534 polymorphism of the IL-2 gene is associated with susceptibility to HSPN in Chinese children.
Keywords: ; ;
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4. Hu X, Tai J, Qu Z, Zhao S, Zhang L, Li M, et al. A Lower Proportion of Regulatory B Cells in Patients with Henoch-Schoenlein Purpura Nephritis. PLoS One. 2016;11(3):e0152368.
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12. Counahan R, Winterborn MH, White RH, Heaton JM, Meadow SR, Bluett NH, et al. Prognosis of Henoch-Schonlein nephritis in children. Br Med J. 1977;2:11-4.
13. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21(2):263-5.
14. Reamy BV, Servey JT, Williams PM. Henoch-Schönlein Purpura (IgA Vasculitis): Rapid Evidence Review. Am Fam Physician. 2020;102(4):229-233.
15. Jelusic M, Sestan M, Cimaz R, Ozen S. Different histological classifications for Henoch-Schönlein purpura nephritis: which one should be used? Pediatr Rheumatol Online J. 2019;17(1):10.
16. Pillebout E, Jamin A, Ayari H, Housset P, Pierre M, Sauvaget V, et al. Biomarkers of IgA vasculitis nephritis in children. PLoS One. 2017;12(11):e0188718.
17. Purevdorj N, Mu Y, Gu Y, Zheng F, Wang R, Yu J, et al. Clinical significance of the serum biomarker index detection in children with Henoch-Schonlein purpura. Clin Biochem. 2018;52:167-70.
18. Pan YX, Ye Q, Shao WX, Shang SQ, Mao JH, Zhang T, et al. Relationship between immune parameters and organ involvement in children with Henoch-Schonlein purpura. PLoS One. 2014;9(12):e115261.
19. Nicoara O, Twombley K. Immunoglobulin A Nephropathy and Immunoglobulin A Vasculitis. Pediatr Clin North Am. 2019;66(1):101-10.
20. Tabel Y, Mir S, Berdeli A. Intleukin 8 gene 2767 A/G polymorphism is associated with increased risk of nephritis in children with Henoch-Schönlein purpura. Rheumatol Int. 2012;32(4):941-947.
21. López-Mejías R, Genre F, Remuzgo-Martínez S, Sevilla Pérez B, Castañeda S, Llorca J, et al: Interleukin 1 beta (IL1ß) rs16944 genetic variant as a genetic marker of severe renal manifestations and renal sequelae in Henoch-Schönlein purpura. Clin Exp Rheumatol. 2016;34(3 Suppl 97):S84-88.
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23. Barış S, Akyürek Ö, Dursun A, Akyol M. The impact of the IL-1β, IL-1Ra, IL-2, IL-6 and IL-10 gene polymorphisms on the development of Behcet's disease and their association with the phenotype. Med Clin (Barc) 2016;146(9):379-83.
24. Fichna M, Żurawek M, Bratland E, Husebye ES, Kasperlik-Załuska A, Czarnocka B, et al. Interleukin-2 and subunit alpha of its soluble receptor in autoimmune Addison's disease--an association study and expression analysis. Autoimmunity. 2015;48(2):100-107.
25. Fedetz M, Ndagire D, Fernandez O, Leyva L, Guerrero M, Arnal C, et al. Multiple sclerosis association study with the TENR-IL2-IL21 region in a Spanish population. Tissue Antigens. 2009;74(3):244-7.
26. Mousa SM, Makhlouf MM, Mohammed ET, Zawam HM. The Influence of Interleukin-2 Gene Polymorphisms on the Risk and Clinical Outcome of Non-Hodgkin Lymphoma. Indian J Hematol Blood Transfus. 2021;37(4):549-54.
27. Wang X, Feng C. The Association between IL2 Genotypes and Risk and Severity of Chronic Periodontitis in a Chinese Han Population: A Case-control Study. Immunol Invest. 2022;51(4):924-930.
28. Yousefi A, Mahmoudi E, Baradaran Noveiry B, Zare Bidoki A, Sadr M, Motamed F, et al. Autoimmune hepatitis association with single nucleotide polymorphism of interleukin-2, but not interferon-gamma. Clin Res Hepatol Gastroenterol. 2018;42(2):134-8.
29. Lee KA, Gay C, Pullinger CR, Hennessy MD, Zak RS, Aouizerat BE. Cytokine polymorphisms are associated with poor sleep maintenance in adults living with human immunodeficiency virus/acquired immunodeficiency syndrome. Sleep. 2014;37(3):453-63.
30. Shumei Y, Yi L, Huanyu M, Zhibin L, Wanlin J, Liqun X, et al. IL-2 gene polymorphisms affect tacrolimus response in myasthenia gravis. Eur J Clin Pharmacol. 2019;75(6):795-800.
31. Timasheva YR, Nasibullin TR, Tuktarova IA, Erdman VV, Galiullin TR, Zaplakhova OV, et al. The analysis of association between multiple sclerosis and genetic markers identified in genome-wide association studies. Zh Nevrol Psikhiatr Im S S Korsakova. 2020;120(7.Vyp.2):54-60. Russian.
2. Chen JY, Mao JH. Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management. World J Pediatr. 2015;11(1):29-34.
3. Dyga K, Szczepańska M. IgA vasculitis with nephritis in children. Adv Clin Exp Med. 2020;29(4):513-519.
4. Hu X, Tai J, Qu Z, Zhao S, Zhang L, Li M, et al. A Lower Proportion of Regulatory B Cells in Patients with Henoch-Schoenlein Purpura Nephritis. PLoS One. 2016;11(3):e0152368.
5. Li B, Ren Q, Ling J, Tao Z, Yang X, Li Y. The change of Th17/Treg cells and IL-10/IL-17 in Chinese children with Henoch-Schonlein purpura: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 2019;98(3):e13991.
6. Pol JG, Caudana P, Paillet J, Piaggio E, Kroemer G. Effects of interleukin-2 in immunostimulation and immunosuppression. J Exp Med. 2020;217(1):e20191247.
7. Visentainer JE, Sell AM, da Silva GC, Cavichioli AD, Franceschi DS, Lieber SR, et al. TNF, IFNG, IL6, IL10 and TGFB1 gene polymorphisms in South and Southeast Brazil. Int J Immunogenet. 2008;35(4-5):287-93.
8. López-Mejías R, Castañeda S, Genre F, Remuzgo-Martínez S, Carmona FD, Llorca J, et al. Genetics of immunoglobulin-A vasculitis (Henoch-Schönlein purpura): An updated review. Autoimmun Rev. 2018;17(3):301-15.
9. Zhernakova A, Alizadeh BZ, Bevova M, van Leeuwen MA, Coenen MJ, Franke B, et al. Novel association in chromosome 4q27 region with rheumatoid arthritis and confirmation of type 1 diabetes point to a general risk locus for autoimmune diseases. Am J Hum Genet. 2007;81(6):1284-8.
10. Maiti AK, Kim-Howard X, Viswanathan P, Guillén L, Rojas-Villarraga A, Deshmukh H, et al. Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus. Arthritis Rheum, 2010;62(2):323-9.
11. Yucel B, Sumer C, Gok I, Karkucak M, Alemdaroglu E, Ucar F. Associations between cytokine gene polymorphisms and rheumatoid arthritis in Turkish population. North Clin Istanb. 2020;11;7(6):563-571.
12. Counahan R, Winterborn MH, White RH, Heaton JM, Meadow SR, Bluett NH, et al. Prognosis of Henoch-Schonlein nephritis in children. Br Med J. 1977;2:11-4.
13. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21(2):263-5.
14. Reamy BV, Servey JT, Williams PM. Henoch-Schönlein Purpura (IgA Vasculitis): Rapid Evidence Review. Am Fam Physician. 2020;102(4):229-233.
15. Jelusic M, Sestan M, Cimaz R, Ozen S. Different histological classifications for Henoch-Schönlein purpura nephritis: which one should be used? Pediatr Rheumatol Online J. 2019;17(1):10.
16. Pillebout E, Jamin A, Ayari H, Housset P, Pierre M, Sauvaget V, et al. Biomarkers of IgA vasculitis nephritis in children. PLoS One. 2017;12(11):e0188718.
17. Purevdorj N, Mu Y, Gu Y, Zheng F, Wang R, Yu J, et al. Clinical significance of the serum biomarker index detection in children with Henoch-Schonlein purpura. Clin Biochem. 2018;52:167-70.
18. Pan YX, Ye Q, Shao WX, Shang SQ, Mao JH, Zhang T, et al. Relationship between immune parameters and organ involvement in children with Henoch-Schonlein purpura. PLoS One. 2014;9(12):e115261.
19. Nicoara O, Twombley K. Immunoglobulin A Nephropathy and Immunoglobulin A Vasculitis. Pediatr Clin North Am. 2019;66(1):101-10.
20. Tabel Y, Mir S, Berdeli A. Intleukin 8 gene 2767 A/G polymorphism is associated with increased risk of nephritis in children with Henoch-Schönlein purpura. Rheumatol Int. 2012;32(4):941-947.
21. López-Mejías R, Genre F, Remuzgo-Martínez S, Sevilla Pérez B, Castañeda S, Llorca J, et al: Interleukin 1 beta (IL1ß) rs16944 genetic variant as a genetic marker of severe renal manifestations and renal sequelae in Henoch-Schönlein purpura. Clin Exp Rheumatol. 2016;34(3 Suppl 97):S84-88.
22. Xu H, Pan Y, Li W, Fu H, Zhang J, Shen H, et al. Association between IL17A and IL17F polymorphisms and risk of Henoch-Schonlein purpura in Chinese children. Rheumatol Int. 2016;36(6):829-35.
23. Barış S, Akyürek Ö, Dursun A, Akyol M. The impact of the IL-1β, IL-1Ra, IL-2, IL-6 and IL-10 gene polymorphisms on the development of Behcet's disease and their association with the phenotype. Med Clin (Barc) 2016;146(9):379-83.
24. Fichna M, Żurawek M, Bratland E, Husebye ES, Kasperlik-Załuska A, Czarnocka B, et al. Interleukin-2 and subunit alpha of its soluble receptor in autoimmune Addison's disease--an association study and expression analysis. Autoimmunity. 2015;48(2):100-107.
25. Fedetz M, Ndagire D, Fernandez O, Leyva L, Guerrero M, Arnal C, et al. Multiple sclerosis association study with the TENR-IL2-IL21 region in a Spanish population. Tissue Antigens. 2009;74(3):244-7.
26. Mousa SM, Makhlouf MM, Mohammed ET, Zawam HM. The Influence of Interleukin-2 Gene Polymorphisms on the Risk and Clinical Outcome of Non-Hodgkin Lymphoma. Indian J Hematol Blood Transfus. 2021;37(4):549-54.
27. Wang X, Feng C. The Association between IL2 Genotypes and Risk and Severity of Chronic Periodontitis in a Chinese Han Population: A Case-control Study. Immunol Invest. 2022;51(4):924-930.
28. Yousefi A, Mahmoudi E, Baradaran Noveiry B, Zare Bidoki A, Sadr M, Motamed F, et al. Autoimmune hepatitis association with single nucleotide polymorphism of interleukin-2, but not interferon-gamma. Clin Res Hepatol Gastroenterol. 2018;42(2):134-8.
29. Lee KA, Gay C, Pullinger CR, Hennessy MD, Zak RS, Aouizerat BE. Cytokine polymorphisms are associated with poor sleep maintenance in adults living with human immunodeficiency virus/acquired immunodeficiency syndrome. Sleep. 2014;37(3):453-63.
30. Shumei Y, Yi L, Huanyu M, Zhibin L, Wanlin J, Liqun X, et al. IL-2 gene polymorphisms affect tacrolimus response in myasthenia gravis. Eur J Clin Pharmacol. 2019;75(6):795-800.
31. Timasheva YR, Nasibullin TR, Tuktarova IA, Erdman VV, Galiullin TR, Zaplakhova OV, et al. The analysis of association between multiple sclerosis and genetic markers identified in genome-wide association studies. Zh Nevrol Psikhiatr Im S S Korsakova. 2020;120(7.Vyp.2):54-60. Russian.
| Files | ||
| Issue | Vol 22 No 3 (2023) | |
| Section | Brief Communication | |
| DOI | https://doi.org/10.18502/ijaai.v22i3.13060 | |
| Keywords | ||
| Henoch-schönlein purpura nephritis Interleukin-2 Polymorphism | ||
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How to Cite
1.
Cao J, Zhang J, Xu H, Li W, Shi J, Ye Q. Association of Interleukin-2 Gene Polymorphism with Henoch-schönlein Purpura Nephritis. Iran J Allergy Asthma Immunol. 2023;22(3):319-326.
