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01-09-2018 | Original Article

ABCB1 gene polymorphism in nephrotic syndrome

Authors: Faten Zahran Mohammed, Mohamed Magdy Zedan, Mona Abo Bakr El-Hussiny, Lamiaa Abd El-Lateaf Ali Barakat, Mohamed Adel Abd El-Motelb El-Eshmawy

Published in: Comparative Clinical Pathology | Issue 5/2018

Abstract

Nephrotic syndrome is the most prevalent glomerular disease in childhood. This study illustrates distribution of the most common three multidrug resistance gene 1 MDR1 (ABCB1) exonic polymorphisms G3435C, G2677 T/A, and C1236T in children with NS to assess their ability to be used as markers for response of NS to steroids. This study aimed to find association between ABCB1 gene polymorphisms and haplotypes and NS and if they can affect their response to steroids. ABCB1 gene polymorphisms in our cases were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Our cases were divided into three groups: one group included 50 steroid sensitive nephrotic syndrome (SSNS) patients, another group included 100 steroid resistant nephrotic syndrome (SRNS) patients, and the third group for 100 age and sex-matched children (control group). ABCB1 C3435T TT, CT + TT genotypes, T allele; ABCB1 G2677A/T GT + GA, TT + AA, GT + GA + TT + AA genotypes, T + A allele frequencies were significantly higher in patients with NS compared to control group. Also, SRNS group showed significantly more frequencies of ABCB1 G2677A/T GT + GA, TT + AA, GT + GA + TT + AA genotypes, T + A allele than SSNS group. TTT + TAT, TTC + TAC haplotype of ABCB1 was also higher in NS patients compared to healthy control subjects. We found that the associations of ABCB1 G2677T/A and C3435T polymorphisms were observed in patients with NS. The ABCB1 G2677 T/A polymorphism was significantly increased in SRNS when compared to SSNS.

Anglicheau D, Flamant M, Schlageter MH, Martinez F, Cassinat B, Beaune P, Legendre C, Thervet E (2003) Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation. Nephrol Dial Transplant 18(11):2409–2414CrossRefPubMed

Bagga A, Mantan M (2005) Nephrotic syndrome in children. Indian J Med Res 122:13–28PubMed

Cascorbi I, Gerloff T, Johne A, Meisel C, Hoffmeyer S, Schwab M, Schaeffeler E, Eichelbaum M, Brinkmann U, Roots I (2001) Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter ABCB1 gene in white subjects. Clin Pharmacol Ther 69:169–174CrossRefPubMed

Chiou YH, Wang LY, Wang TH, Huang SP (2012) Genetic polymorphisms influence the steroid treatment of children with idiopathic nephritic syndrome. Pediatr Nephrol 27(9):1511–1517CrossRefPubMed

Choi HJ, Cho HY, Ro H, Lee SH, Han KH, Lee H, Kang HG, Ha IS, Choi Y, Cheong HI (2011) Polymorphisms of the ABCB1 and MIF genes in children with nephrotic syndrome. Pediatr Nephrol 26(11):1981–1988CrossRefPubMed

Cizmarikova M, Podracka L, Klimcakova L, Habalova V, Boor A, Mojzis J, Mirossay L (2015) ABCB1 polymorphisms and idiopathic nephrotic syndrome in Slovak children: preliminary results. Med Sci Monit 21:59–68CrossRefPubMedPubMedCentral

Dilger K, Schwab M, Fromm MF (2004) Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 10:578–583CrossRefPubMed

Eichelbaum M, Fromm MF, Schwab M (2004) Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Ther Drug Monit 26:180–185CrossRefPubMed

El Bakkali L, Rodrigues PR, Kuik DJ, Ket JC, Van Wijk JA (2011) Nephrotic syndrome in the Netherlands: a population-based cohort study and a review of the literature. Pediatr Nephrol l26:1241–1246CrossRef

Gumus-Akay G, Rustemoglu A, Karadag A, Sunguroglu A (2008) Genotype and allele frequencies of ABCB1 gene C1236T polymorphism in a Turkish population. Genet Mol Res 7:1193–1199CrossRefPubMed

Ieiri I, Takane H, Otsubo K (2004) The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clin Pharmacokinet 43:553–576CrossRefPubMed

Jafar T, Prasad N, Agarwal V, Mahdi A, Gupta A, Sharma RK, Negi MP, Agrawal S (2011) ABCB1 gene polymorphisms in steroid-responsive versus steroid resistant nepherotic syndrome in children. Nephrol Dial Transplant 26(12):3968–3974CrossRefPubMed

Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI, Taylor A, Xie HG, McKinsey J, Zhou S, Lan LB, Schuetz JD, Schuetz EG, Wilkinson GR (2001) Identification of functionally variant ABCB1 alleles among European Americans and African Americans. Clin Pharmacol Ther 70:189–199CrossRefPubMed

Kim HJ, Hwang SY, Kim JH, Park HJ, Lee SG, Lee SW, Joo JC, Kim YK (2009) Association between genetic polymorphism of multidrug resistance 1 gene and Sasang constitutions. Evid Based Complement Alternat Med 6(1):73–80CrossRefPubMedPubMedCentral

Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM (2007) A “silent” polymorphism in the ABCB1 gene changes substrate specificity. Science 315:525–528CrossRefPubMed

Kroetz DL, Pauli-Magnus C, Hodges LM, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, DeYoung J, Taylor T, Carlson EJ, Herskowitz I, Giacomini KM, Clark AG (2003) Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics 13:481–494CrossRefPubMed

Kurzawski M, Pawlik A, Gornik W, Drozdzik M (2006) Frequency of common ABCB1 gene variants in a Polish population. Pharmacol Rep 58:35–40PubMed

Kuwano M, Uchiumi T, Hayakawa H, Ono M, Wada M, Izumi H, Kohno K (2003) The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis related factors in human malignancies. Cancer Sci 94:9–14CrossRefPubMed

Mortazavi F, Khiavi YS (2011) Steroid response pattern and outcome of pediatric idiopathic nephrotic syndrome: a single-center experience in Northwest Iran. Ther Clin Risk Manag 7:167–171CrossRefPubMedPubMedCentral

Orlowska-Kowalik G, Malecka-Massalska T, Ksiazek A (2008) Elevated serum CA-125 levels in a patient with nephroticsyndrome. Am J Case Rep 9:351–354

Sakaeda T (2005) ABCB1 genotype-related pharmacokinetics: fact or fiction? Drug. Metab Pharmacokinet 20:391–414CrossRef

Sakaeda T, Nakamura T, Okumura K (2004) Pharmacogenetics of drug transporters and its impact on the pharmacotherapy. Curr Top Med Chem 4:1385–1398CrossRefPubMed

Schwab M, Eichelbaum M, Fromm MF (2003) Genetic polymorphisms of the human ABCB1 drug transporter. Annu Rev Pharmacol Toxicol 43:285–307CrossRefPubMed

Siegsmund M, Brinkmann U, Scháffeler E, Weirich G, Schwab M, Eichelbaum M, Fritz P, Burk O, Decker J, Alken P, Rothenpieler U, Kerb R, Hoffmeyer S, Brauch H (2002) Association of the P-glycoprotein transporter ABCB1(C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol 13:1847–1854CrossRefPubMed

Skalova S, Podhola M, Vondrak K, Chernin G (2010) Plasma pheresis-induced clinical improvement in a patient with steroid-resistant nephrotic syndrome due to podocin (NPHS2) gene mutation. Acta Med (Hradec Kralové) 53(3):157–159CrossRef

Sukhai M, Piquette-Miller M (2000) Regulation of the multidrug resistance genes by stress signals. J Pharm Pharm Sci 3:268–280PubMed

Suvanto M, Jahnukainen T, Kestilä M, Jalanko H (2016) Single nucleotide polymorphisms in pediatric idiopathic nephrotic syndrome. Int J Nephrol 2016:1–12CrossRef

Takane H, Kobayashi D, Hirota T, Kigawa J, Terakawa N, Otsubo K, Ieiri I (2004) Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene. J Pharmacol Exp Ther 311:1179–1187CrossRefPubMed

Teeninga N, Kist-van Holthe JE, van Rijswijk N, de Mos NI, Hop WCI, Wetzels JFM, van der Heijden AJ, Nauta J (2013) Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol 24:149–159CrossRefPubMed

Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, Komano T, Hori R (1992) Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem 267:24248–24252PubMed

Wasilewska A, Zalewski G, Chyczewski L, Zoch-Zwierz W (2007) ABCB1 gene polymorphismsand clinical course of steroid-responsive nephritic syndrome in children. Pediatr Nephrol 22:44–51CrossRefPubMed

Woodahl EL, Ho RJ (2004) The role of ABCB1 genetic polymorphisms in interindividual variability in P-glycoprotein expression and function. Curr Drug Metab 5:11–19CrossRefPubMed

Xu P, Jiang ZP, Zhang BK, Tu JY, Li HD (2008) Impact of ABCB1 haplotypes derived from C1236T, G2677T/A and C3435T on the pharmacokinetics of single dose oral digoxin in healthy Chinese volunteers. Pharmacology 82:221–227CrossRefPubMed

Youssef DM, Attia TA, El-Shal AS, Abduelometty FA (2013) Multi-drug resistance-1 gene polymorphisms in nephritic syndrome: impact on susceptibility and response to steroids. Gene 530(2):201–207CrossRefPubMed

Title: ABCB1 gene polymorphism in nephrotic syndrome
Authors: Faten Zahran Mohammed
Mohamed Magdy Zedan
Mona Abo Bakr El-Hussiny
Lamiaa Abd El-Lateaf Ali Barakat
Mohamed Adel Abd El-Motelb El-Eshmawy
Publication date: 01-09-2018
Publisher: Springer London
Published in: Comparative Clinical Pathology / Issue 5/2018
Print ISSN: 1618-5641
Electronic ISSN: 1618-565X
DOI: https://doi.org/10.1007/s00580-018-2719-0

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ABCB1 gene polymorphism in nephrotic syndrome

Abstract

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Abstract

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