Generic placeholder image

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Research Article

Evaluation of Immunity-related GTPase Family M Protein (IRGM) SNPs among Egyptian Lupus Patients: A Case-control Study

Author(s): Ahmed Y. Ali, Basma M. Medhat, Sara S. Ashour, Amul M. Badr, Dalia Dorgham, Hala Ramadan and Mervat E. Behiry*

Volume 19, Issue 4, 2023

Published on: 02 May, 2023

Page: [463 - 469] Pages: 7

DOI: 10.2174/1573397119666230330081708

Price: $65

Abstract

Objective: One of the potential factors that cause systemic lupus erythematosus (SLE) development is autophagy. Immunity-related GTPase family M protein (IRGM) has been shown to be linked to immune-mediated diseases. The aim of the current study was to assess the role of the IRGM-autophagy gene in SLE susceptibility in an Egyptian population and its relation to lupus nephritis.

Methods: A case-control study was conducted in which a total of 200 subjects (100SLE and 100 healthy controls) were enrolled. Two single-nucleotide polymorphisms (SNPs) (rs10065172 and rs4958847) were genotyped. Genotypes and alleles analysis was conducted to compare between cases and controls, as well as a stratification analysis was conducted on the presence or absence of lupus nephritis.

Results: Among selected SNPs of IRGM, no association was found between both SNPs and SLE susceptibility. For rs10065172, the major expressed genotype was CC (61% and 71%) (Adj OR= 2.9, 95%= 0.545-15.5), followed by TC (34% and 27%) (Adj OR= 1.985, 95% = 0.357-11.041) in cases and controls, respectively. For rs4958847, AA and AG were comparably expressed in case [(43% and 39%) (Adj OR= 1.073, 95% = 0.483-2.382)] and control [(41% and 43%) (Adj OR= 1.24, 95% = 0.557- 2.763)], respectively. Additionally, no relationship among both SNPs and gender, lupus nephritis, disease activity, or disease duration, was observed.

Conclusion: IRGM SNPs (rs10065172 and rs4958847) expression was comparable among SLE patients and controls of the Egyptian cohort. Genotype and allele frequency of IRGM SNPs did not differ in lupus nephritis and non-lupus nephritis patients.

[1]
Teruel M, Alarcón-Riquelme ME. The genetic basis of systemic lupus erythematosus: What are the risk factors and what have we learned. J Autoimmun 2016; 74: 161-75.
[http://dx.doi.org/10.1016/j.jaut.2016.08.001] [PMID: 27522116]
[2]
Alexander JC, Ursula E, Andrea C, et al. Autophagy is activated in systemic lupus erythematosus and required for plasmablast development. Ann Rheum Dis 2015; 74: 912-20.
[http://dx.doi.org/10.1136/annrheumdis-2013-204343] [PMID: 24419333]
[3]
Wang L, Law H. The role of autophagy in lupus nephritis. Int J Mol Sci 2015; 16(10): 25154-67.
[http://dx.doi.org/10.3390/ijms161025154] [PMID: 26506346]
[4]
Yao Q, Zhu Y, Wang W, et al. Polymorphisms in autophagy-related gene IRGM are associated with susceptibility to autoimmune thyroid diseases. BioMed Res Int 2018; 2018: 1-7.
[http://dx.doi.org/10.1155/2018/7959707] [PMID: 29992164]
[5]
Harley JB, Alarcón-Riquelme ME, Criswell LA, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008; 40(2): 204-10.
[http://dx.doi.org/10.1038/ng.81] [PMID: 18204446]
[6]
López P, Alonso-Pérez E, Rodríguez-Carrio J, Suárez A. Influence of Atg5 mutation in SLE depends on functional IL-10 genotype. PLoS One 2013; 8(10): e78756.
[http://dx.doi.org/10.1371/journal.pone.0078756] [PMID: 24205307]
[7]
Lee YK, Lee JA. Role of the mammalian ATG8/LC3 family in autophagy: Differential and compensatory roles in the spatiotemporal regulation of autophagy. BMB Rep 2016; 49(8): 424-30.
[http://dx.doi.org/10.5483/BMBRep.2016.49.8.081] [PMID: 27418283]
[8]
Zhou X, Lu X, Lv J, et al. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis 2011; 70(7): 1330-7.
[http://dx.doi.org/10.1136/ard.2010.140111] [PMID: 21622776]
[9]
Perricone C, Iagnocco A, Ceccarelli F, et al. AB0164 ATG5 RS573755 is protective of erosive damage evaluated by musculo-skeletal ultrasound in patients with systemic lupus erythematosus. Ann Rheum Dis 2015; 74 (Suppl. 2): 9452.
[http://dx.doi.org/10.1136/annrheumdis-2015-eular.4924]
[10]
Kamel AM, Badary MS, Mohamed WA, Ahmed GH, El-Feky MA. Evaluation of autophagy‐related genes in Egyptian systemic lupus erythematosus patients. Int J Rheum Dis 2020; 23(9): 1226-32.
[http://dx.doi.org/10.1111/1756-185X.13910] [PMID: 32783391]
[11]
Kim BH, Shenoy AR, Kumar P, Bradfield CJ, MacMicking JD. IFN-inducible GTPases in host cell defense. Cell Host Microbe 2012; 12(4): 432-44.
[http://dx.doi.org/10.1016/j.chom.2012.09.007] [PMID: 23084913]
[12]
Yang Z, Goronzy JJ, Weyand CM. Autophagy in autoimmune disease. J Mol Med 2015; 93(7): 707-17.
[http://dx.doi.org/10.1007/s00109-015-1297-8] [PMID: 26054920]
[13]
Rai P, Janardhan KS, Meacham J, et al. IRGM1 links mitochondrial quality control to autoimmunity. Nat Immunol 2021; 22(3): 312-21.
[http://dx.doi.org/10.1038/s41590-020-00859-0] [PMID: 33510463]
[14]
Wu DJ, Adamopoulos IE. Autophagy and autoimmunity. Clin Immunol 2017; 176: 55-62.
[http://dx.doi.org/10.1016/j.clim.2017.01.007] [PMID: 28095319]
[15]
Perl A. Metabolic and mitochondrial dysfunction in SLE Lahita’s systemic lupus erythematosus. Cambridge, UK: Academic Press 2021; pp. 109-16.
[http://dx.doi.org/10.1016/B978-0-12-820583-9.00014-2]
[16]
Pisetsky DS, Spencer DM, Mobarrez F, Fuzzi E, Gunnarsson I, Svenungsson E. The binding of SLE autoantibodies to mitochondria. Clin Immunol 2020; 212: 108349.
[http://dx.doi.org/10.1016/j.clim.2020.108349] [PMID: 31982644]
[17]
Nath P, Jena KK, Mehto S, et al. IRGM links autoimmunity to autophagy. Autophagy 2021; 17(2): 578-80.
[http://dx.doi.org/10.1080/15548627.2020.1810920] [PMID: 32813580]
[18]
Jena KK, Mehto S, Nath P, et al. Autoimmunity gene IRGM suppresses cGAS ‐ STING and RIG ‐I‐ MAVS signaling to control interferon response. EMBO Rep 2020; 21(9): e50051.
[http://dx.doi.org/10.15252/embr.202050051] [PMID: 32715615]
[19]
Rioux JD, Xavier RJ, Taylor KD, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 2007; 39(5): 596-604.
[http://dx.doi.org/10.1038/ng2032] [PMID: 17435756]
[20]
Ru FS, Ciccacci C, Di FD. Autophagy and inflammatory bowel disease: Association between variants of the autophagy related IRGM gene and susceptibility to Crohn’s disease. Dig Liver Dis 2015; 47(9): 744-50.
[http://dx.doi.org/10.1016/j.dld.2015.05.012] [PMID: 26066377]
[21]
Moon CM, Shin DJ, Kim SW, et al. Associations between genetic variants in the IRGM gene and inflammatory bowel diseases in the Korean population. Inflamm Bowel Dis 2013; 19(1): 106-14.
[http://dx.doi.org/10.1002/ibd.22972] [PMID: 22508677]
[22]
Baskaran K, Pugazhendhi S, Ramakrishna BS. Association of IRGM gene mutations with inflammatory bowel disease in the Indian population. PLoS One 2014; 9(9): e106863.
[http://dx.doi.org/10.1371/journal.pone.0106863] [PMID: 25191865]
[23]
Xia Q, Wang M, Yang X, et al. Autophagy-related IRGM genes confer susceptibility to ankylosing spondylitis in a Chinese female population: A case–control study. Genes Immun 2017; 18(1): 42-7.
[http://dx.doi.org/10.1038/gene.2016.48] [PMID: 28031552]
[24]
Hochberg MC. Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40(9): 1725.
[http://dx.doi.org/10.1002/art.1780400928] [PMID: 9324032]
[25]
Gladman DD, Goldsmith CH, Urowitz MB, et al. The systemic lupus international collaborating clinics/american college of rheumatology (slicc/acr) damage index for systemic lupus erythematosus international comparison. J Rheumatol 2000; 27(2): 373-6.
[PMID: 10685799]
[26]
Yin H, Wu H, Chen Y, et al. The therapeutic and pathogenic role of autophagy in autoimmune diseases. Front Immunol 2018; 9: 1512.
[http://dx.doi.org/10.3389/fimmu.2018.01512] [PMID: 30108582]
[27]
Kuballa P, Nolte WM, Castoreno AB, Xavier RJ. Autophagy and the immune system. Annu Rev Immunol 2012; 30(1): 611-46.
[http://dx.doi.org/10.1146/annurev-immunol-020711-074948] [PMID: 22449030]
[28]
Martinez J, Cunha LD, Park S, et al. RETRACTED ARTICLE: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells. Nature 2016; 533(7601): 115-9.
[http://dx.doi.org/10.1038/nature17950] [PMID: 27096368]
[29]
Ajayi TA, Innes CL, Grimm SA, et al. Crohn’s disease IRGM risk alleles are associated with altered gene expression in human tissues. Am J Physiol Gastrointest Liver Physiol 2019; 316(1): G95-G105.
[http://dx.doi.org/10.1152/ajpgi.00196.2018] [PMID: 30335469]
[30]
Li D, Guo B, Wu H, Tan L, Chang C, Lu Q. Interleukin-17 in systemic lupus erythematosus: A comprehensive review. Autoimmunity 2015; 48(6): 353-61.
[http://dx.doi.org/10.3109/08916934.2015.1037441] [PMID: 25894789]
[31]
Yilmaz N, Yazici A, Özulu Türkmen B, Karalok I. Yavuz Ş. Sacroiliitis in systemic lupus erythematosus revisited. Arch Rheumatol 2020; 35(2): 254-8.
[http://dx.doi.org/10.46497/ArchRheumatol.2020.7514] [PMID: 32851375]
[32]
Yang W, Tang H, Zhang Y, et al. Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians. Am J Hum Genet 2013; 92(1): 41-51.
[http://dx.doi.org/10.1016/j.ajhg.2012.11.018] [PMID: 23273568]
[33]
Freedman BI, Langefeld CD, Andringa KK, et al. End-stage renal disease in African Americans with lupus nephritis is associated with APOL1. Arthritis Rheumatol 2014; 66(2): 390-6.
[http://dx.doi.org/10.1002/art.38220] [PMID: 24504811]
[34]
Zhou X, Nath SK, Qi Y, et al. Brief Report: Identification of MTMR3 as a novel susceptibility gene for lupus nephritis in northern Han Chinese by shared-gene analysis with IgA nephropathy. Arthritis Rheumatol 2014; 66(10): 2842-8.
[http://dx.doi.org/10.1002/art.38749] [PMID: 24943867]
[35]
Wu MY, Wang EJ, Feng D, Li M, Ye RD, Lu JH. Pharmacological insights into autophagy modulation in autoimmune diseases. Acta Pharm Sin B 2021; 11(11): 3364-78.
[http://dx.doi.org/10.1016/j.apsb.2021.03.026] [PMID: 34900523]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy