Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis

Abstract

Background

The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17 A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the IL-17A gene; nevertheless, the findings have been conflicting. We conducted a meta-analysis that included previously published reports to establish a definitive conclusion on the role of the IL-17A rs2275913 polymorphism in SLE propensity.

Materials and Methods

The PubMed, Google Scholar, and Scopus databases were used to find eligible published articles. All analyses were conducted using Comprehensive Meta-analysis V3.1. Funnel plots and Egger’s regression analysis were used to assess publication bias. Q statistics and I² test explored the heterogeneity among the included studies. Combined odds ratio, 95% confidence interval were calculated for each comparison model.

Results

Based on the inclusion and exclusion criteria, a total of four reports, comprising of 608 SLE patients and 815 healthy controls, were considered for the present meta-analysis. The homozygous comparison (AA vs. GG: combined odds ratio= 2.046, p = 0.005) and recessive genetic model (AA vs. GG+GA: combined odds ratio=1.901, p = 0.010) analysis revealed a significant association of rs2275913 with susceptibility to the development of SLE. However, other genetic comparisons (A vs. G, GA vs. GG, AA+GA vs. GG) failed to demonstrate such association. Furthermore, trial sequential analysis revealed a sufficient number of studies, including enough cases and controls that have already been considered to conclude the role of IL17-A rs2275913 polymorphism in SLE.

Conclusions

IL-17A rs2275913 polymorphism is associated with susceptibility to SLE development.

Keywords

meta-analysis interleukin-17A systemic lupus erythematosus rs2275913 genetic predisposition

Get full access to this article

View all access options for this article.

References

Fortuna

Brennan

. Systemic lupus erythematosus. Dental Clin North America 2013; 57: 631–655. DOI: 10.1016/j.cden.2013.06.003.

Tsokos

. Systemic lupus erythematosus. New Engl J Med 2011; 365: 2110–2121. DOI: 10.1056/NEJMra1100359.

Petri

. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2002; 16: 847–858.

Brinks

Hoyer

Weber

, et al. Age-specific and sex-specific incidence of systemic lupus erythematosus: an estimate from cross-sectional claims data of 2.3 million people in the German statutory health insurance 2002. Lupus Sci Med 2016; 3: e000181–e000181. DOI: 10.1136/lupus-2016-000181.

Barber

MRW

Drenkard

Falasinnu

, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol 2021; 17: 515–532. DOI: 10.1038/s41584-021-00668-1.

Dean

Tyrrell-Price

Crawley

, et al. Cytokines and systemic lupus erythematosus. Ann Rheum Dis 2000; 59: 243–251. DOI: 10.1136/ard.59.4.243.

Vukelic

Laloo

Kyttaris

. Interleukin 23 is elevated in the serum of patients with SLE. Lupus 2020; 29: 1943–1947. DOI: 10.1177/0961203320952841.

Ding

You

, et al. Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis. Clinics 2020; 75: e1801–e1801. DOI: 10.6061/clinics/2020/e1801.

McGeachy

Bak-Jensen

Chen

, et al. TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nat Immunology 2007; 8: 1390–1397.

10.

Lochner

Wang

Sparwasser

. The special relationship in the development and function of T helper 17 and regulatory T cells. Prog Molecular Biology Translational Science 2015; 136: 99–129.

11.

Kang

H-K

Liu

Datta

. Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of inflammatory Th17 cells. J Immunol 2007; 178: 7849–7858.

12.

Abdel Galil

Ezzeldin

El-Boshy

. The role of serum IL-17 and IL-6 as biomarkers of disease activity and predictors of remission in patients with lupus nephritis. Cytokine 2015; 76: 280–287. DOI: 10.1016/j.cyto.2015.05.007.

13.

Chen

Deng

, et al. Plasma IL-17A is increased in new-onset SLE patients and associated with disease activity. J Clin Immunol 2010; 30: 221–225. DOI: 10.1007/s10875-009-9365-x.

14.

Dedong

Feiyan

Jie

, et al. Analysis of interleukin-17 and interleukin-23 for estimating disease activity and predicting the response to treatment in active lupus nephritis patients. Immunol Lett 2019; 210: 33–39. DOI: 10.1016/j.imlet.2019.04.002.

15.

Talaat

Mohamed

Bassyouni

, et al. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: CORRELATION with disease activity. Cytokine 2015; 72: 146–153. DOI: 10.1016/j.cyto.2014.12.027.

16.

Jiang

Sun

, et al. The plasma interleukin (IL)-35 level and frequency of circulating IL-35+ Regulatory B cells are decreased in a cohort of chinese patients with new-onset systemic lupus erythematosus. Scientific Reports 2019; 9: 13210. DOI: 10.1038/s41598-019-49748-z.

17.

Panda

Das

. Diminished IL-17A levels may protect filarial-infected individuals from development of rheumatoid arthritis and systemic lupus erythematosus. Lupus 2017; 26: 348–354. DOI: 10.1177/0961203316662722.

18.

Abou Ghanima

Elolemy

Ganeb

, et al. Role of T helper 17 cells in the pathogenesis of systemic lupus erythematosus. Egypt Journal Immunology 2012; 19: 25–33.

19.

Chen

Wan

. Altered frequency of Th17 and Treg cells in new-onset systemic lupus erythematosus patients. Eur Journal Clinical Investigation 2018; 48: e13012. DOI: 10.1111/eci.13012.

20.

Kamanu

Medvedeva

Schaefer

, et al. Mutations and Binding Sites of Human Transcription Factors. Front GeneticsOriginal Res 2012; 3. DOI: 10.3389/fgene.2012.00100.

21.

Tseng

C-C

Wong

M-C

Liao

W-T

, et al. Genetic variants in transcription factor binding sites in humans: triggered by natural selection and triggers of diseases. Int J Mol Sci 2021; 22: 4187.

22.

Stafforini

. Functional consequences of mutations and polymorphisms in the coding region of the PAF acetylhydrolase (PAF-AH) Gene. Pharmaceuticals 2009; 2: 94–117. DOI: 10.3390/ph2030094.

23.

Ghaznavi

Soltanpour

. Association study between rs2275913 genetic polymorphism and serum levels of IL-17A with risk of coronary artery disease. Mol Bio Res Comm 2020; 9: 35–40. DOI: 10.22099/mbrc.2020.35442.1463.

24.

Lang

Liu

Hou

, et al. IL-17A polymorphism (rs2275913) and levels are associated with preeclampsia pathogenesis in Chinese patients. BMC Medical Genomics 2021; 14: 5. DOI: 10.1186/s12920-020-00840-8.

25.

Elkoumi

Allah

Mohamed

, et al. Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study. Lupus 2020; 29: 767–775. DOI: 10.1177/0961203320922305.

26.

Huang

H-T

Y-L

Wang

, et al. The association of IL-17A polymorphisms with IL-17A serum levels and risk of ischemic stroke. Oncotarget 2017; 8: 103499–103508. DOI: 10.18632/oncotarget.21498.

27.

Pasha

Tantawy

Youssef

. Osteopontin and interleukin-17A genes polymorphisms in Egyptian systemic lupus erythematosus patients: a relation to disease activity and severity. Gene 2019; 702: 107–113.

28.

Sharifzadeh

Naeimi

Nasiri

, et al. IL-17A gene polymorphism at position G197A and systemic lupus erythematosus. Rheumatol Res 2018; 3: 107–112.

29.

Montúfar‐Robles

Barbosa‐Cobos

Alemán‐Ávila

, et al. IL‐17A haplotype confers susceptibility to systemic lupus erythematosus but not to rheumatoid arthritis in Mexican patients. Int Journal Rheumatic Diseases 2019; 22: 473–479.

30.

Hristova

Kamenarska

Dzhebir

, et al. The role of IL-17 rs2275913, IL-17RC rs708567 and TGFB1 rs1800469 SNPs and IL-17A serum levels in patients with lupus nephritis. Rheumatol Int 2021; 41: 2205–2213.

31.

Lee

. Meta-analysis of genetic association studies. Ann Lab Med 2015; 35: 283–287. DOI: 10.3343/alm.2015.35.3.283.

32.

Wells

Shea

O’Connell

, et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Oxford, 2000.

33.

Faul

Erdfelder

Buchner

, et al. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Research Methods 2009; 41: 1149–1160.

34.

Lee

. Meta-analysis of genetic association studies. Ann Laboratory Medicine 2015; 35: 283–287.

35.

Egger

Smith

Schneider

, et al. Bias in meta-analysis detected by a simple, graphical test. Bmj 1997; 315: 629–634. DOI: 10.1136/bmj.315.7109.629.

36.

Melsen

Bootsma

MCJ

Rovers

, et al. The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses. Clin Microbiol Infect 2014; 20: 123–129, DOI: 10.1111/1469-0691.12494.

, et al. The association between G-197A gene polymorphism of IL-17A with changes in protein interaction of IL-17A, levels of urinary IL-17, and degree of lupus nephritis abnormality. Comp Clin Pathol 2016; 25: 535–541.

38.

Lee

Song

. Associations between circulating interleukin-17 levels and systemic lupus erythematosus and between Interleukin-17 gene polymorphisms and disease susceptibility: a meta-analysis. J Rheum Dis 2020; 27: 37–44.

, et al. Interleukin-17Ars2275913, Interleukin-17Frs763780 and rs2397084 gene polymorphisms as possible risk factors in Juvenile lupus and lupus related nephritis. Autoimmunity 2016; 49: 31–40.

, et al. Juvenile lupus: Different clinical and serological presentations compared to adult lupus in Egypt. The Egypt Rheumatologist 2018; 40: 55–58, DOI: 10.1016/j.ejr.2017.04.004 .

. Crucial role for nuclear factor of activated T cells in T cell receptor-mediated regulation of human interleukin-17. J Biol Chem 2004; 279: 52762–52771. DOI: 10.1074/jbc.M405764200.

42.

Dong

Shi

, et al. IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Chin Medical Journal 2003; 116: 543–548.

43.

Lee

Seo

, et al. Inhibition of IL-17 ameliorates systemic lupus erythematosus in Roquinsan/san mice through regulating the balance of TFH cells, GC B cells, Treg and Breg. Scientific Reports 2019; 9: 5227–5228.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.08 MB

0.04 MB