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2000
Volume 21, Issue 5
  • ISSN: 1573-3971
  • E-ISSN: 1875-6360

Abstract

Introduction/Objectives

Genetic variations could explain individual responses to drugs. This case-control study aimed to investigate the association between the multidrug resistance 1 () gene exonic single nucleotide variants (SNVs), and , and the response to intravenous methylprednisolone in Egyptian patients with active systemic lupus erythematosus (SLE).

Methods

Real-time polymerase chain reaction was used. Patients were divided into responders and resistant based on the SLE Disease Activity Index (SLEDAI). The degree of improvement was determined according to a 7-point Likert scale.

Results

The study included 80 patients: 40 patients with renal flares and 40 patients with extrarenal flares. In patients with extrarenal flares, 71.4% of responders had the CT+TT model of the variant 36.8% of resistant patients ( = 0.028); the T allele was detected in 47.6% of responders 23.7% of resistant patients ( = 0.026). Patients with the TT and CT genotypes, TT+CT model, and T allele of the variant had significant improvement based on the Likert scale compared with the CC genotype, CC model and C allele ( = 0.049, 0.038, 0.010 and <0.001, respectively). In the renal subgroup, patients with the CC genotype and C allele of the C3435T variant had significant improvement based on the Likert scale compared with the CT genotype and T allele ( = 0.028 and 0.046, respectively). Patients with the CC model had significantly lower post-treatment proteinuria compared with the TT+CT model ( = 0.024).

Conclusion

C1236T variant allele and C3435T wild allele seem to enhance the response to glucocorticoids in Egyptian patients with active SLE.

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References

  1. CrowM.K. FiresteinG.S. BuddR.C. GabrielS.E. McInnesL.B. O’DellJ.R. Etiology and Pathogenesis of Systemic Lupus Erythematosus.Kelley and Firestein’s Textbook of Rheumatology.ElsevierPhiladelphia, PA20171329134410.1016/B978‑0‑323‑31696‑5.00079‑6
     [Google Scholar]
  2. JacobsJ.W.J. BijlsmaJ.W.J. Glucocorticoid therapy.Eds. Kelley and Firestein’s Textbook of Rheumatology. Philadelphia, PA: Elsevier 2009; 863-81.10.1016/B978‑0‑323‑31696‑5.00060‑7
     [Google Scholar]
  3. GrossK.L. LuN.Z. CidlowskiJ.A. Molecular mechanisms regulating glucocorticoid sensitivity and resistance.Mol. Cell. Endocrinol.20093001-271610.1016/j.mce.2008.10.00119000736
     [Google Scholar]
  4. MartinsC.S. de CastroM. Generalized and tissue specific glucocorticoid resistance.Mol. Cell. Endocrinol.202153011127710.1016/j.mce.2021.11127733864884
     [Google Scholar]
  5. van de VenR. OerlemansR. van der HeijdenJ.W. SchefferG.L. de GruijlT.D. JansenG. ScheperR.J. ABC drug transporters and immunity: Novel therapeutic targets in autoimmunity and cancer.J. Leukoc. Biol.20098651075108710.1189/jlb.030914719745159
     [Google Scholar]
  6. Kyle-CezarF. Echevarria-LimaJ. GoldenbergR.C.S. RumjanekV.M. Expression of c-kit and Sca-1 and their relationship with multidrug resistance protein 1 in mouse bone marrow mononuclear cells.Immunology2007121112212810.1111/j.1365‑2567.2007.02547.x17425603
     [Google Scholar]
  7. PawlikA. WrzesniewskaJ. Fiedorowicz-FabrycyI. Gawronska-SzklarzB. The MDR1 3435 polymorphism in patients with rheumatoid arthritis.Int. J. Clin. Pharmacol. Ther.200442949650310.5414/CPP4249615487808
     [Google Scholar]
  8. WangJ. LiuY. ZhaoJ. XuJ. LiS. QinX. P-glycoprotein gene MDR1 polymorphisms and susceptibility to systemic lupus erythematosus in Guangxi population: A case-control study.Rheumatol. Int.201737453754510.1007/s00296‑017‑3652‑228154898
     [Google Scholar]
  9. YangQ.F. ChenB.L. ZhangQ.S. ZhuZ.H. HuB. HeY. GaoX. WangY.M. HuP.J. ChenM.H. ZengZ.R. Contribution of MDR1 gene polymorphisms on IBD predisposition and response to glucocorticoids in IBD in a Chinese population.J. Dig. Dis.2015161223010.1111/1751‑2980.1220525346426
     [Google Scholar]
  10. XuanM. LiH. FuR. YangY. ZhangD. ZhangX. YangR. Association of ABCB1 gene polymorphisms and haplotypes with therapeutic efficacy of glucocorticoids in Chinese patients with immune thrombocytopenia.Hum. Immunol.201475431732110.1016/j.humimm.2014.01.01324486577
     [Google Scholar]
  11. WasilewskaA. ZalewskiG. ChyczewskiL. Zoch-ZwierzW. MDR-1 gene polymorphisms and clinical course of steroid-responsive nephrotic syndrome in children.Pediatr. Nephrol.2007221445110.1007/s00467‑006‑0275‑317043887
     [Google Scholar]
  12. OzenF. SilanC. UludagA. CandanF. SilanF. OzdemirS. AtikS. OzdemirO. Association between ABCB1 (MDR1) gene 3435 C>T polymorphism and colchicine unresponsiveness of FMF patients.Ren. Fail.201133989990310.3109/0886022X.2011.60598021851199
     [Google Scholar]
  13. MuralidharanN. AntonyP.T. JainV.K. MariaselvamC.M. NegiV.S. Multidrug resistance 1 (MDR1) 3435C>T gene polymorphism influences the clinical phenotype and methotrexate-induced adverse events in South Indian Tamil Rheumatoid arthritis.Eur. J. Clin. Pharmacol.201571895996510.1007/s00228‑015‑1885‑026071279
     [Google Scholar]
  14. MendozaJ.L. UrcelayE. LanaR. MartínC.M. LópezN. GuijarroL.G. MayolJ.A. TaxoneraC. de la Conchae.g. PeñaA.S. Díaz-RubioM. MDR1 polymorphisms and response to azathioprine therapy in patients with Crohnʼs disease.Inflamm. Bowel Dis.200713558559010.1002/ibd.2004417262810
     [Google Scholar]
  15. AnglicheauD. VerstuyftC.C.A.A. Laurent-PuigP. BecquemontL. SchlageterM.H.C.A.A.C.G.A. CassinatB. BeauneP. LegendreC. ThervetE. Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients.J. Am. Soc. Nephrol.20031471889189610.1097/01.ASN.0000073901.94759.3612819250
     [Google Scholar]
  16. PetriM. OrbaiA.M. AlarcónG.S. GordonC. MerrillJ.T. FortinP.R. BruceI.N. IsenbergD. WallaceD.J. NivedO. SturfeltG. Ramsey-GoldmanR. BaeS.C. HanlyJ.G. Sánchez-GuerreroJ. ClarkeA. AranowC. ManziS. UrowitzM. GladmanD. KalunianK. CostnerM. WerthV.P. ZomaA. BernatskyS. Ruiz-IrastorzaG. KhamashtaM.A. JacobsenS. BuyonJ.P. MaddisonP. DooleyM.A. van VollenhovenR.F. GinzlerE. StollT. PeschkenC. JorizzoJ.L. CallenJ.P. LimS.S. FesslerB.J. InancM. KamenD.L. RahmanA. SteinssonK. FranksA.G.Jr SiglerL. HameedS. FangH. PhamN. BreyR. WeismanM.H. McGwinG.Jr MagderL.S. Derivation and validation of the systemic Lupus international collaborating clinics classification criteria for systemic lupus erythematosus.Arthritis Rheum.20126482677268610.1002/art.3447322553077
     [Google Scholar]
  17. BombardierC. GladmanD.D. UrowitzM.B. CaronD. ChangC.H. AustinA. BellA. BlochD.A. CoreyP.N. DeckerJ.L. EsdaileJ. FriesJ.F. GinzlerE.M. GoldsmithC.H. HochbergM.C. JonesJ.V. RicheN.G.H.L. LiangM.H. LockshinM.D. MuenzL.R. SackettD.L. SchurP.H. Derivation of the sledai. A disease activity index for lupus patients.Arthritis Rheum.199235663064010.1002/art.17803506061599520
     [Google Scholar]
  18. CuppenB.V.J. PardaliK. KraanM.C. MarijnissenA.C.A. YrlidL. OlssonM. BijlsmaJ.W.J. LafeberF.P.J.G. Fritsch-StorkR.D.E. Polymorphisms in the multidrug-resistance 1 gene related to glucocorticoid response in rheumatoid arthritis treatment.Rheumatol. Int.201737453153610.1007/s00296‑017‑3653‑128132103
     [Google Scholar]
  19. GladmanD.D. UrowitzM.B. KagalA. HallettD. Accurately describing changes in disease activity in Systemic Lupus Erythematosus.J. Rheumatol.200027237737910685800
     [Google Scholar]
  20. Calculator of Hardy-Weinberg equilibrium2023Available from: http://wpcalc.com/en/equilibrium-hardy-weinberg/
  21. Your web tool for SNP analysis.2023Available from: https://www.snpstats.net/start.htm
  22. SakaedaT. MDR1 genotype-related pharmacokinetics: Fact or fiction?Drug Metab. Pharmacokinet.200520639141410.2133/dmpk.20.39116415525
     [Google Scholar]
  23. Kimchi-SarfatyC. OhJ.M. KimI.W. SaunaZ.E. CalcagnoA.M. AmbudkarS.V. GottesmanM.M. A “silent” polymorphism in the MDR1 gene changes substrate specificity.Science2007315581152552810.1126/science.113530817185560
     [Google Scholar]
  24. SunF. CaoB.Q. WangB. WuS.Q. JiangD.H. Association between ABCB1 genetic polymorphism and the effect on epilepsy following phenytoin treatment.Exp. Ther. Med.20161231780178410.3892/etm.2016.355327602091
     [Google Scholar]
  25. ShenX. ChengJ. Effects of MDR1 (C3435T) polymorphism on resistance, uptake, and efflux to antiepileptic drugs.DNA Cell Biol.201938325025510.1089/dna.2018.455330632789
     [Google Scholar]
  26. LiM. XuM. LiuW. GaoX. Effect of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of tacrolimus in the treatment of nephrotic syndrome.BMC Pharmacol. Toxicol.20181911410.1186/s40360‑018‑0202‑929615122
     [Google Scholar]
  27. JiangB. YanL. WuQ. ABCB1 (C1236T) polymorphism affects P-glycoprotein- mediated transport of methotrexate, doxorubicin, actinomycin D, and etoposide.DNA Cell Biol.201938548549010.1089/dna.2018.458330977678
     [Google Scholar]
  28. KrupovesA. MackD. SeidmanE. DeslandresC. AmreD. Associations between variants in the ABCB1 (MDR1) gene and corticosteroid dependence in children with Crohnʼs disease.Inflamm. Bowel Dis.201117112308231710.1002/ibd.2160821987299
     [Google Scholar]
  29. JafarT. PrasadN. AgarwalV. MahdiA. GuptaA. SharmaR.K. NegiM.P.S. AgrawalS. MDR-1 gene polymorphisms in steroid-responsive versus steroid-resistant nephrotic syndrome in children.Nephrol. Dial. Transplant.201126123968397410.1093/ndt/gfr15021460357
     [Google Scholar]
  30. DaiY. NiS. WuF. GuoS. ZhaoX. WangJ. ABCB1 gene polymorphisms impact the effect of high-dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4-IgG -positive neuromyelitis optica spectrum disorder.J. Clin. Pharm. Ther.20224791379138710.1111/jcpt.1367535488449
     [Google Scholar]
  31. PrasadS. TripathiD. RaiM.K. AggarwalS. MittalB. AgarwalV. Multidrug resistance protein-1 expression, function and polymorphisms in patients with rheumatoid arthritis not responding to methotrexate.Int. J. Rheum. Dis.201417887888610.1111/1756‑185X.1236224734954
     [Google Scholar]
  32. ChiouY.H. WangL.Y. WangT.H. HuangS. Genetic polymorphisms influence the steroid treatment of children with idiopathic nephrotic syndrome.Pediatr. Nephrol.20122791511151710.1007/s00467‑012‑2182‑022610055
     [Google Scholar]
  33. ChoiH.J. ChoH.Y. RoH. LeeS.H. HanK.H. LeeH. KangH.G. HaI.S. ChoiY. CheongH.I. Polymorphisms of the MDR1 and MIF genes in children with nephrotic syndrome.Pediatr. Nephrol.201126111981198810.1007/s00467‑011‑1903‑021553324
     [Google Scholar]
  34. SafanM.A. ElhelbawyN.G. MidanD.A. KhaderH.F. ABCB1 polymorphisms and steroid treatment in children with idiopathic nephrotic syndrome.Br. J. Biomed. Sci.2017741364110.1080/09674845.2016.122070727719329
     [Google Scholar]
  35. HanS.S. XuY.Q. LuY. GuX.C. WangY. A PRISMA-compliant meta-analysis of MDR1 polymorphisms and idiopathic nephrotic syndrome.Medicine (Baltimore)20179624e719110.1097/MD.000000000000719128614261
     [Google Scholar]
  36. KimR. LeakeB.F. ChooE.F. DresserG.K. KubbaS.V. SchwarzU.I. TaylorA. XieH.G. McKinseyJ. ZhouS. LanL.B. SchuetzJ.D. SchuetzE.G. WilkinsonG.R. Identification of functionally variant MDR1 alleles among European Americans and African Americans.Clin. Pharmacol. Ther.200170218919910.1067/mcp.2001.11741211503014
     [Google Scholar]
  37. GanesanA, Mini Jacob S, Arvind Selvin Kumar R, Padmaraj R, Anandan B, Sambantham S. Identification of functional single nucleotide polymorphisms of multidrug resistance gene-1 among nephrotic syndrome children in South India.Asian J. Pharm. Clin. Res.2017102418422
     [Google Scholar]
  38. SiegmundW. LudwigK. GiessmannT. DazertP. SchroederE. SperkerB. WarzokR. KroemerH.K. CascorbiI. The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol.Clin. Pharmacol. Ther.200272557258310.1067/mcp.2002.12773912426521
     [Google Scholar]
  39. OselinK. Nowakowski-GashawI. MrozikiewiczP.M. WolbergsD. PähklaR. RootsI. Quantitative determination of MDR1 mRNA expression in peripheral blood lymphocytes: A possible role of genetic polymorphisms in the MDR1 gene.Eur. J. Clin. Invest.200333326126710.1046/j.1365‑2362.2003.01133.x12641546
     [Google Scholar]
  40. DrozdzikM. RudasT. PawlikA. KurzawskiM. CzernyB. GornikW. HerczynskaM. The effect of 3435C>T MDR1 gene polymorphism on Rheumatoid arthritis treatment with disease-modifying antirheumatic drugs.Eur. J. Clin. Pharmacol.2006621193393710.1007/s00228‑006‑0192‑116932953
     [Google Scholar]
  41. SkalskiD. WendorffJ. RomanowiczH. RyszA. MarchelA. StasiołekM. SmolarzB. Associations between MDR1 C3435T polymorphism and drug-resistant epilepsy in the Polish population.Acta Neurol. Belg.2017117115315810.1007/s13760‑016‑0690‑627534401
     [Google Scholar]
  42. HeH. YinJ.Y. XuY.J. LiX. ZhangY. LiuZ.G. ZhouF. ZhaiM. LiY. LiX.P. WangY. ZhouH.H. LiuZ.Q. Association of ABCB1 polymorphisms with the efficacy of ondansetron in chemotherapy-induced nausea and vomiting.Clin. Ther.201436812421252.e210.1016/j.clinthera.2014.06.01625012726
     [Google Scholar]
  43. HoffmeyerS. BurkO. von RichterO. ArnoldH.P. BrockmöllerJ. JohneA. CascorbiI. GerloffT. RootsI. EichelbaumM. BrinkmannU. Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo .Proc. Natl. Acad. Sci. USA20009773473347810.1073/pnas.97.7.347310716719
     [Google Scholar]
  44. HitzlM. DrescherS. van der KuipH. SchäffelerE. FischerJ. SchwabM. EichelbaumM. FrommM.F. The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells.Pharmacogenetics200111429329810.1097/00008571‑200106000‑0000311434506
     [Google Scholar]
  45. SalamaN.N. YangZ. BuiT. HoR.J.Y. MDR1 haplotypes significantly minimize intracellular uptake and transcellular P-gp substrate transport in recombinant LLC-PK1 cells.J. Pharm. Sci.200695102293230810.1002/jps.2071716883550
     [Google Scholar]
  46. XuP. JiangZ.P. ZhangB.K. TuJ.Y. LiH.D. Impact of MDR1 haplotypes derived from C1236T, G2677T/A and C3435T on the pharmacokinetics of single-dose oral digoxin in healthy Chinese volunteers.Pharmacology200882322122710.1159/00015648818810246
     [Google Scholar]
  47. TakaneH. KobayashiD. HirotaT. KigawaJ. TerakawaN. OtsuboK. IeiriI. Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene.J. Pharmacol. Exp. Ther.200431131179118710.1124/jpet.104.06972415280437
     [Google Scholar]
  48. MagedL.A. MagdyM. MahmoudG.A. Is it time to switch to low dose pulsed Methylprednisolone for treatment of flares in Systemic Lupus Erythematosus?HIV Nursing20232310761083
     [Google Scholar]
  49. AkdoganM.R. MelikogluM.A. A potential biomarker of disease activity in systemic lupus erythematosus, systemic immune-inflammation index.North. Clin. Istanb.202411211511910.14744/nci.2023.9013238757099
     [Google Scholar]
  50. LiangP. TangY. LinL. ZhongH. YangH. ZengY. LvJ. LiX. LuY. XuA. Low level of circulating basophil counts in biopsy-proven active lupus nephritis.Clin. Rheumatol.201837245946510.1007/s10067‑017‑3858‑428988406
     [Google Scholar]
  51. DossybayevaK. BexeitovY. MukushevaZ. AlmukhamedovaZ. AssylbekovaM. AbdukhakimovaD. RakhimzhanovaM. PoddigheD. Analysis of peripheral blood basophils in pediatric Systemic Lupus Erythematosus.Diagnostics (Basel)2022127170110.3390/diagnostics1207170135885605
     [Google Scholar]
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Influence of Multidrug Resistance 1 Gene Variants on Response to Intravenous Methylprednisolone Pulse in Systemic Lupus Erythematosus Patients: Preliminary Results
Curr. Rheumatol. Rev. 21, 581 (2025); https://doi.org/10.2174/0115733971345970241107114732
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Supplementary Material 1: Detailed genotyping and Real Time PCR techniques. Supplementary Material 2: A flow chart for the selection and enrollment of patients. Table Demographics, comorbidities, disease characteristics and system-based disease flares of the study cohort Table Comparisons between responders and resistant patients regarding pre-treatment characteristics. Table Laboratory features and disease activity scores prior to intravenous pulse methylprednisolone in patients with different genotypes, models and alleles of the multidrug-resistance 1 gene () C1236T and C3435T variants. Supplementary material is available on the publisher’s website along with the published article.

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  • Article Type:     Research Article
Keyword(s): glucocorticoids; multidrug resistance 1 gene, (MDR1) gene, C1236T variant, TT+CT model; Systemic lupus erythematosus

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