Association Between Null Genotypes of Glutathione S-Transferase M1 and T1 and Susceptibility to Systemic Lupus Erythematosus: A Meta-Analysis
Abstract
Oxidative stress is involved in the development of systemic lupus erythematosus (SLE). It is well known that activity of the glutathione S-transferase superfamily has a protective effect against oxidative stress. Several studies have investigated the association between the GSTT1/GSTM1 polymorphisms and the risk of SLE with inconsistent results. The present meta-analysis was performed to investigate the association between susceptibility to SLE and the null genotypes of GSTT1 and GSTM1. Eligible publications were identified by searching several databases, 18 case-control studies with 2483 cases and 3643 controls met the inclusion criteria. The raw data of three reports have internal inconsistencies, therefore these studies were excluded from the final analysis. The results showed that the GSTM1 null genotype significantly increased the risk of SLE (OR = 1.17, 95 % CI: 1.03-1.32, p = 0.012) with no evidence of significant heterogeneity (Q = 14.53, df = 14, p = 0.411; I² = 3.4 %). The GSTT1 null genotype was not associated with the risk of SLE (OR = 0.94, 95 % CI: 0.80-1.10, p = 0.447). There was no evidence of heterogeneity between studies. The present study showed that the null genotype of GSTM1 was weakly associated with the risk of SLE.
References
Yan Z, Chen Q, Xia Y. Oxidative stress contributes to inflammatory and cellular damage in systemic lupus erythematosus: cellular markers and molecular mechanism. J Inflamm Res. 2023 Feb 4;16:453-65. doi: 10.2147/JIR.S399284.
Shah D, Mahajan N, Sah S, Nath SK, Paudyal B. Oxidative stress and its biomarkers in systemic lupus erythematosus. J Biomed Sci. 2014 Mar 17;21(1):23. doi: 10.1186/1423-0127-21-23.
Bae SC, Lee YH. Associations between paraoxonase-1 and systemic lupus erythematosus. Lupus. 2019 Nov;28(13):1571-6. doi: 10.1177/0961203319884653.
Sam NB, Li BZ, Leng RX, Pan HF, Ye DQ. Circulating antioxidant levels in systemic lupus erythematosus patients: a systematic review and meta-analysis. Biomark Med. 2019 Sep;13(13):1137-52. doi: 10.2217/bmm-2019-0034.
Block SR, Winfield JB, Lockshin MD, D'Angelo WA, Christian CL. Studies of twins with systemic lupus erythematosus. A review of the literature and presentation of 12 additional sets. Am J Med. 1975 Oct;59(4):533-52. doi: 10.1016/0002-9343(75)90261-2.
Lahita RG, Chiorazzi N, Gibofsky A, Winchester RJ, Kunkel HG. Familial systemic lupus erythematosus in males. Arthritis Rheum. 1983 Jan;26(1):39-44. doi: 10.1002/art.1780260107.
Kuo CF, Grainge MJ, Valdes AM, See LC, Luo SF, Yu KH, et al. Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families. JAMA Intern Med. 2015 Sep;175(9):1518-26. doi: 10.1001/jamainternmed.2015.3528.
Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30(6):445-600. doi: 10.3109/10409239509083491.
Mazari AMA, Zhang L, Ye ZW, Zhang J, Tew KD, Townsend DM. The multifaceted role of glutathione s-transferases in health and disease. Biomolecules. 2023 Apr 18;13(4):688. doi: 10.3390/biom13040688.
Li Y, Li L, Fan D, Wang Z, Cui Y. Effects of GST null genotypes on individual susceptibility to atherosclerotic cardiovascular diseases: a meta-analysis. Free Radic Res. 2020 Sep;54(8-9):567-73. doi: 10.1080/10715762.2019.1624743.
Saadat M. Null genotypes of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms increased susceptibility to type 2 diabetes mellitus, a meta-analysis. Gene. 2013 Dec 10;532(1):160-2. doi: 10.1016/j.gene.2013.08.079.
Kumar KV, Goturi A, Nagaraj M, Goud EVSS. Null genotypes of Glutathione S-transferase M1 and T1 and risk of oral cancer: A meta-analysis. J Oral Maxillofac Pathol. 2022 Oct-Dec;26(4):592. doi: 10.4103/jomfp.jomfp_435_21.
Song L, Yang C, He XF. Individual and combined effects of GSTM1 and GSTT1 polymorphisms on colorectal cancer risk: an updated meta-analysis. Biosci Rep. 2020 Aug 28;40(8):BSR20201927. doi: 10.1042/BSR20201927.
Liu H, Xu Y, Peng J. Glutathione S-transferase M1/T1 polymorphisms and schizophrenia risk: a new method for quality assessment and a systematic review. Neuropsychiatr Dis Treat. 2023 Jan 7;19:97-107. doi: 10.2147/NDT.S376942.
Lee YH, Seo YH, Kim JH, Choi SJ, Ji JD, Song GG. Meta-analysis of associations between MTHFR and GST polymorphisms and susceptibility to multiple sclerosis. Neurol Sci. 2015 Nov;36(11):2089-96. doi: 10.1007/s10072-015-2318-7.
Ji JD, Lee WJ. Association between the polymorphisms of glutathione S-transferase genes and rheumatoid arthritis: a meta-analysis. Gene. 2013 May 25;521(1):155-9. doi: 10.1016/j.gene.2013.03.023.
Su X, Ren Y, Li M, Kong L, Kang J. Association of glutathione S-transferase M1 and T1 genotypes with asthma: A meta-analysis. Medicine (Baltimore). 2020 Aug 21;99(34):e21732. doi: 10.1097/MD.0000000000021732.
Abbas M, Verma S, Verma S, Siddiqui S, Khan FH, Raza ST, et al. Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome. J Med Virol. 2021 Sep;93(9):5446-51. doi: 10.1002/jmv.27076.
Saadat M. An evidence for correlation between the glutathione S-transferase T1 (GSTT1) polymorphism and outcome of COVID-19. Clin Chim Acta. 2020 Sep;508:213-6. doi: 10.1016/j.cca.2020.05.041.
de Oliveira MAA, Mallmann NH, de Souza GKBB, de Jesus Bacha T, Lima ES, de Lima DSN, et al. Glutathione S-transferase, catalase, and mitochondrial superoxide dismutase gene polymorphisms modulate redox potential in systemic lupus erythematosus patients from Manaus, Amazonas, Brazil. Clin Rheumatol. 2021 Sep;40(9):3639-49. doi: 10.1007/s10067-021-05680-0.
Jevtovic Stoimenov T, Despotovic M, Stojanovic S, Basic J, Pavlovic D. Polymorphic variants of antioxidative defense enzymes and their gene-gene epistatic interactions in systemic lupus erythematode patients. Clin Rheumatol. 2017 Sep;36(9):2019-26. doi: 10.1007/s10067-017-3755-x.
Salimi S, Nakhaee A, Jafari M, Jahantigh D, Sandooghi M, Zakeri Z, et al. Combination effect of GSTM1, GSTT1 and GSTP1 polymorphisms and risk of systemic lupus erythematosus. Iran J Public Health. 2015 Jun;44(6):814-21. PMID: 26258094.
Glesse N, Rohr P, Monticielo OA, Rech TF, Brenol JC, Xavier RM, et al. Genetic polymorphisms of glutathione S-transferases and cytochrome P450 enzymes as susceptibility factors to systemic lupus erythematosus in southern Brazilian patients. Mol Biol Rep. 2014 Sep;41(9):6167-79. doi: 10.1007/s11033-014-3496-8.
Rupasree Y, Naushad SM, Rajasekhar L, Kutala VK. Association of genetic variants of xenobiotic metabolic pathway with systemic lupus erythematosus. Indian J Biochem Biophys. 2013 Oct;50(5):447-52. PMID: 24772967.
Zhang J, Deng J, Zhang C, Lu Y, Liu L, Wu Q, et al. Association of GSTT1, GSTM1 and CYP1A1 polymorphisms with susceptibility to systemic lupus erythematosus in the Chinese population. Clin Chim Acta. 2010 Jun 3;411(11-12):878-81. doi: 10.1016/j.cca.2010.03.007.
Kang TY, El-Sohemy A, Comelis MC, Eny KM, Bae SC. Glutathione S-transferase genotype and risk of systemic lupus erythematosus in Koreans. Lupus. 2005;14(5):381-4. doi: 10.1191/0961203305lu2100oa.
Fraser PA, Ding WZ, Mohseni M, Treadwell EL, Dooley MA, St Clair EW, et al. Glutathione S-transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: a possible gene-environment interaction for autoimmunity. J Rheumatol. 2003 Feb;30(2):276-82. PMID: 12563680.
Ollier W, Davies E, Snowden N, Alldersea J, Fryer A, Jones P, Strange R. Association of homozygosity for glutathione-S-transferase GSTM1 null alleles with the Ro+/La- autoantibody profile in patients with systemic lupus erythematosus. Arthritis Rheum. 1996 Oct;39(10):1763-4. doi: 10.1002/art.1780391023.
Kiyohara C, Washio M, Horiuchi T, Asami T, Ide S, Atsumi T, et al; Kyushu Sapporo SLE (KYSS) Study Group. Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of cigarette smoking and systemic lupus erythematosus in a Japanese population. Scand J Rheumatol. 2012 Mar;41(2):103-9. doi: 10.3109/03009742.2011.608194.
Nasr AS, Darweesh H, El Khateeb E, Fayed HL, El-Drakony AH. Role of glutathione S-transferases polymorphisms and monocytes CD64 expression in Egyptian patients with systemic lupus erythematosus. Egypt Rheumatol. 2017;39:139-43. doi: 10.1016/j.ejr.2017.04.001.
Tew MB, Ahn CW, Friedman AW, Reveille JD, Tan FK, Alarcón GS, et al. Systemic lupus erythematosus in three ethnic groups. VIII. Lack of association of glutathione S-transferase null alleles with disease manifestations. Arthritis Rheum. 2001 Apr;44(4):981-3. doi: 10.1002/1529-0131(200104)44:4<981::AID-ANR158>3.0.CO;2-0.
Horiuchi T, Washio M, Kiyohara C, Tsukamoto H, Tada Y, Asami T, et al; Kyushu Sapporo SLE Study Group. Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and the risk of Japanese SLE: findings from the KYSS study. Rheumatology (Oxford). 2009 Sep;48(9):1045-9. doi: 10.1093/rheumatology/kep166.
Lu L, Lei D, Nong X, Guo M, Ma J, He L. The null polymorphism of the GSTM1/T1 gene is not associated with susceptibility to systemic lupus erythematosus: a meta-analysis. Mol Diagn Ther. 2015 Feb;19(1):65-9. doi: 10.1007/s40291-015-0131-x.
Lee YH, Song GG. Association between glutathione S-transferase M1, P1, and NFKB1 polymorphisms and systemic lupus erythematosus susceptibility: a meta-analysis. Cell Mol Biol (Noisy-le-grand). 2016 Sep 30;62(11):21-6. PMID: 27755947.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986 Sep;7(3):177-88. doi: 10.1016/0197-2456(86)90046-2.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48. PMID: 13655060.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997 Sep 13;315(7109):629-34. doi: 10.1136/bmj.315.7109.629.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002 Jun 15;21(11):1539-58. doi: 10.1002/sim.1186.
Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N. Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst. 2004 Mar 17;96(6):434-42. doi: 10.1093/jnci/djh075.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).