Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 17:33:141-151.
doi: 10.1016/j.jare.2021.02.001. eCollection 2021 Nov.

Assessment of the Link of ABCB1 and NR3C1 gene polymorphisms with the prednisolone resistance in pediatric nephrotic syndrome patients of Bangladesh: A genotype and haplotype approach

Most Nazma Parvin  1   2 , Md Abdul Aziz  3 , Sikder Nahidul Islam Rabbi  4 , Mir Md Abdullah Al-Mamun  1 , Mohammed Hanif  5 , Md Saiful Islam  1 , Mohammad Safiqul Islam  3
Affiliations

Assessment of the Link of ABCB1 and NR3C1 gene polymorphisms with the prednisolone resistance in pediatric nephrotic syndrome patients of Bangladesh: A genotype and haplotype approach

Most Nazma Parvin et al. J Adv Res. .

Abstract

Introduction: Nephrotic syndrome is a common pediatric kidney disease. Investigations on several genetic polymorphisms revealed an inconsistent influence on the resistance of patients to steroids.

Objectives: This study aimed to identify the association of ABCB1 (1236C > T, 2677G > T, 3435C > T), NR3C1 (rs10482634, rs6877893), and CYP3A5 (CYP3A5*3) gene polymorphism as well as sociodemographic and clinicopathological parameters with the risk of developing prednisolone resistance in pediatric patients with nephrotic syndrome.

Methods: A case-control analysis was performed on 180 nephrotic syndrome patients. Among them, 30 patients were classified as prednisolone resistant group, and 150 were classified as prednisolone sensitive group. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: No significant association of 1236C > T polymorphism with the risk of prednisolone resistance (p > 0.05) was found. The GT heterozygous of 2677G > T was found to be significantly associated with the development of prednisolone resistance (OR = 3.9, p = 0.034). In the case of 3435C > T, a statistically significant association was observed in TC heterozygous and TT mutant homozygous genotypes (OR = 0.38, p = 0.047; OR = 3.06, p = 0.038, respectively) with prednisolone resistance. For rs10482634 polymorphism, the AG heterozygous and AG+GG genotypes were significantly linked with prednisolone resistance (OR = 2.40, p = 0.033; OR = 2.36, p = 0.034, respectively). We found no association with the risk of prednisolone resistance with rs6877893 and CYP3A5*3 polymorphism (p > 0.05). CTC and TGT haplotypes of ABCB1 and GA haplotype of NR3C1 were also associated with the increased risk of pediatric prednisolone resistance (OR = 4.47, p = 0.0003; OR = 2.71, p = 0.03; and OR = 4.22, p = 0.022, consecutively). We also observed the correlation of different sociodemographic and clinicopathological factors with prednisolone resistance in pediatric nephrotic syndrome.

Conclusion: Our findings showed a significant association of ABCB1 and NR3C1 gene polymorphisms with prednisolone resistant pediatric nephrotic syndrome.

Keywords: 95%CI, 95% confidence intervals; ABCB1; CYP3A5; GC, Glucocorticoids; GR, Glucocorticoid receptor; HWE, Hardy-Weinberg equilibrium; LD, Linkage disequilibrium; MDR1, multidrug resistance gene 1; MesPGN, mesangioproliferative glomerulonephritis; NR3C1; NR3C1, nuclear receptor subfamily 3, group C, member 1; NS, Nephrotic syndrome; Nephrotic syndrome; OR, odds ratio; P-gp, Permeability glycoprotein; PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; PR, Prednisolone resistance; PRG, Prednisolone resistance group; PRNS, Prednisolone resistance nephrotic syndrome; PSG, Prednisolone sensitive group; Pharmacogenetics; Prednisolone resistance; SRNS, steroid-resistance nephrotic syndrome; SSNS, Steroid-sensitive nephrotic syndrome.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
D′ and r2 values generated from the haplotyping of rs1128503, rs2032582, and rs1045642 SNPs in case-control combined group.
Fig. 2
Fig. 2
Fig. 1: D′ and r2 values generated from the haplotyping rs10482634 and rs6877893 SNPs in the case-control combined group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nawaz Z., Mushtaq F., Mousa D. Pattern of glomerular disease in the Saudi population: A single-center, five-year retrospective study. Saudi J Kidney Dis Transplant. 2013;24(6):1265. - PubMed
    1. Bagga A. Management of steroid resistant nephrotic syndrome. Indian Pediatr. 2009;46(1) - PubMed
    1. Levine S.A. In: Brenner & Rector's The Kidney. 7th ed. Brenner B.M., Floyd C., editors. WB Saunders; Philadelphia: 2003. Nephrotic Syndrome; pp. 297–313.
    1. Gordillo R., Spitzer A. The nephrotic syndrome. Pediatr Rev. 2009;30(3):94. - PubMed
    1. Schijvens A.M., ter Heine R., De Wildt S.N. Pharmacology and pharmacogenetics of prednisone and prednisolone in patients with nephrotic syndrome. Pediatr Nephrol. 2019;34(3):389–403. - PMC - PubMed

Publication types

Substances