A POSSIBLE ASSOCIATION OF ABCB1 (MDR1) GENE rs1045642 VARIANT (SNP) WITH THE DEVELOPMENT OF RENAL GLOMERULAR DISEASES

Öz

Objective: Renal glomerular disease is an issue that causes proteinuria, edema, and sometimes hematuria and associated with tiny filters in the kidney called glomerulus. In this retrospective study, we aimed to analyze the possible association of renal glomerular diseases with the ABCB1 (MDR1) gene C3435T poly- morphism (rs1045642), with respect to their genetic basis.
Material and Methods: A total of 52 cases with renal glomerular disease were compared with 58 healthy controls for the ABCB1 C3435T polymorphism screened by strip assay and NGS. Allele frequencies and ge- notype distributions of the relevant gene variant were analyzed.
Results: The patient group included focal segmental glomerulosclerosis, membranous glomerulonephritis, IgA nephropathy, diabetic nephropathy, amyloidosis, and similar conditions. The C allele (wild type) and CC genotype of the MDR1 C3435T single nucleotide polymorphism (SNP) were higher in the control group compared to patients, while the T allele (mutant type) and TT genotype were significantly higher in patient group than controls. The patients were older than the healthy controls.
Conclusion: ABCB1 (MDR1) C3435T polymorphism cause a decrease in P-glycoprotein function. In this context, our data suggests that the C3435T variant (SNP) contributes to the development of renal glomerular diseases.

Anahtar Kelimeler

• Renal Glomerular Disease
• ABCB1 Gene
• Polymorphism
• P-glycoprotein

Etik Beyan

Ethics committee approval was received from the Health Sciences Research Ethics Committee of Sivas Cumhuriyet University (Date of decision: 24.04.2025 and approval number: 2025-04/22). The study was carried out in accordance with the Declaration of Helsinki.

ABCB1 (MDR1) Geni rs1045642 Varyantının (SNP) Renal Glomeruler Hastalık Gelişimiyle Olası Bir İlişkisi

Öz

Amaç: Renal glomerüler hastalık, proteinüri, ödem ve bazen hematüriye neden olan ve böbrekte glomeru- lus adı verilen küçük filtrelerle ilişkili bir sorundur. Biz bu retrospektif çalışmada, renal glomerüler hastalık- ların ABCB1 (MDR1) geni C3435T polimorfizmi (rs1045642) ile olası ilişkisini, genetik temelleri bağlamında analiz etmeyi amaçladık.
Gereç ve Yöntemler: Renal glomerüler hastalığı olan toplam 52 vaka, strip assay ve NGS ile taranan ABCB1 C3435T polimorfizmi açısından 58 sağlıklı kontrol ile karşılaştırıldı. İlgili gen varyantının alel frekansları ve genotip dağılımları analiz edildi.
Bulgular: Hasta grubunda fokal segmental glomeruloskleroz, membranöz glomerulonefrit, IgA nefropatisi, diyabetik nefropati, amiloidoz ve benzeri rahatsızlıklar yer alıyordu. MDR1 C3435T tek nükleotid polimor- fizminin (SNP) C aleli (doğal tip) ve CC genotipi kontrol grubunda hastalara göre daha yüksek bulunurken, T aleli (mutant tip) ve TT genotipi hasta grubunda kontrollere kıyasla anlamlı olarak daha yüksek çıktı. Hastalar sağlıklı kontrollerden daha yaşlıydı.
Sonuç: ABCB1 (MDR1) C3435T polimorfizmi P-glikoprotein fonksiyonunda azalmaya neden olmaktadır. Bu bağlamda, verilerimiz C3435T varyantının (SNP) renal glomerüler hastalıkların gelişimine katkıda bulunduğunu düşündürmektedir.

Anahtar Kelimeler

• Renal Glomeruler Hastalık
• ABCB1 Geni
• Polimorfizm
• P-glikoprotein

Kaynakça

1. 1. Wang CS, Greenbaum LA. Nephrotic Syndrome. Pediatr Clin North Am. 2019;66(1):73-85.
2. 2. Liebeskind DS. Nephrotic syndrome. Handb Clin Neurol. 2014:119:405-15.
3. 3. Kodner C. Diagnosis and Management of Nephrotic Syndrome in Adults. Am Fam Physician. 2016;93(6):479-85.
4. 4. Vivarelli M, Massella L, Ruggiero B, Emma F. Minimal Change Disease. Clin J Am Soc Nephrol. 2016;12(2):332–45.
5. 5. Bărar AA, Pralea IE, Maslyennikov Y, Munteanu R, Berindan-Neagoe I, Pîrlog R, et al. Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics. Int J Mol Sci. 2024;25(11):5613.
6. 6. Nagata M, Kobayashi N, Hara S. Focal segmental glomerulosclerosis; why does it occur segmentally? Pflugers Arch. 2017;469(7-8):983-8.
7. 7. Gleeson PJ, O'Shaughnessy MM, Barratt J. IgA nephropathy in adults-treatment standard. Nephrol Dial Transplant. 2023;38(11):2464-73.
8. 8. Dantas M, Silva LBB, Pontes BTM, Dos Reis MA, de Lima PSN, Moysés Neto M. Membranous nephropathy. J Bras Nefrol. 2023;45(2):229-43.

9. 9. Samsu N. Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed Res Int. 2021;2021:1497449.
10. 10. Murashima R, Sai E, Tagawa Y, Yanagawa H, Ishiwata S, Kawaguchi Y, et al. Usefulness of Dapagliflozin for Nephrotic Syndrome Secondary to Diabetic Kidney Disease. Intern Med. 2022;61(24):3699-702.
11. 11. Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2017;12(5):825-35.
12. 12. Rowczenio DM, Youngstein T, Trojer H, Omoyinmi E, Baginska A, Brogan P, et al. British kindred with dominant FMF associated with high incidence of AA amyloidosis caused by novel MEFV variant, and a review of the literature. Rheumatology (Oxford). 2020;59(3):554-8.
13. 13. Jamroziak K, Robak T. Pharmacogenomics of MDR1/ABCB1 gene: the influence on risk and clinical outcome of haematological malignancies. Hematology. 2004;9(2):91-105.
14. 14. Chai AB, Callaghan R, Gelissen IC. Regulation of P-Glycoprotein in the Brain. Int J Mol Sci. 2022;23(23):14667.
15. 15. Mijac D, Vukovic-Petrovic I, Mijac V, Perovic V, Milic N, Djuranovic S, et al. MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease. PLoS One. 2018;13(3):e0194536.
16. 16. Ahmed SS, Husain RS, Kumar S, Ramakrishnan V. Association between MDR1 gene polymorphisms and Parkinson's disease in Asian and Caucasian populations: a meta-analysis. J Neurol Sci. 2016;368:255-62.
17. 17. Woodahl EL, Ho RJ. The role of MDR1 genetic polymorphisms in interindividual variability in P-glycoprotein expression and function. Curr Drug Metab. 2004;5(1):11-9.
18. 18. Parsa Nahad M, Makvandi M, Teimoori A, Jalilian S, Kayedani GA, Mahmoodi S. MDR1 gene C3435T polymorphism in chronic hepatitis C patients. Microb Pathog. 2018;114:63-7.
19. 19. Sakaeda T, Nakamura T, Okumura K. MDR1 genotype-related pharmacokinetics and pharmacodynamics. Biol Pharm Bull. 2002;25(11):1391-400.
20. 20. Youssef DM, Attia TA, El-Shal AS, Abduelometty FA. Multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: impact on susceptibility and response to steroids. Gene. 2013;530(2):201-7.
21. 21. Brinar M, Cukovic-Cavka S, Bozina N, Ravic KG, Markos P, Ladic A, et al. MDR1 polymorphisms are associated with inflammatory bowel disease in a cohort of Croatian IBD patients. BMC Gastroenterol. 2013;13:57.
22. 22. Jeleń AM, Sałagacka A, Żebrowska MK, Mirowski M, Talarowska M, Gałecki P, et al. The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report. Int J Med Sci. 2015 Nov 20;12(12):974-9.
23. 23. Sheng X, Zhang L, Tong N, Luo D, Wang M, Xu M, et al. MDR1 C3435T polymorphism and cancer risk: a meta-analysis based on 39 case-control studies. Mol Biol Rep. 2012;39(7):7237-49.
24. 24. Wang J, Wang B, Bi J, Li K, Di J. MDR1 gene C3435T polymorphism and cancer risk: a meta-analysis of 34 case-control studies. J Cancer Res Clin Oncol. 2012;138(6):979-89.
25. 25. Shabaka A, Tato Ribera A, Fernández-Juárez G. Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective. Nephron. 2020;144(9):413-27.
26. 26. Altintas MM, Agarwal S, Sudhini Y, Zhu K, Wei C, Reiser J. Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders. Annu Rev Pathol. 2025;20(1):329-53.
27. 27. Rosenberg AZ, Kopp JB. Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol. 2017;12(3):502-17.
28. 28. De Vriese AS, Sethi S, Nath KA, Glassock RJ, Fervenza FC. Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach. J Am Soc Nephrol. 2018;29(3):759-74.
29. 29. Taherkhani A, Nafar M, Arefi-Oskouie A, Broumandnia N, Parvin M, Mahmoudieh L, et al. Metabolomic Analysis of Membranous Glomerulonephritis: Identification of a Diagnostic Panel and Pathogenic Pathways. Arch Med Res. 2019;50(4):159-69.
30. 30. Villacorta J, Ortego S, Moreno E, Saiz A, Alonso M, Fernandez-Lucas M, et al. Membranous glomerulonephritis with masked deposits. Nefrologia (Engl Ed). 2023;43(5):653-54.
31. 31. Rajasekaran A, Julian BA, Rizk DV. IgA Nephropathy: An Interesting Autoimmune Kidney Disease. Am J Med Sci. 2021;361(2):176-94.
32. 32. Filippone EJ, Gulati R, Farber JL. Contemporary review of IgA nephropathy. Front Immunol. 2024;15:1436923.
33. 33. Waikhom R, Sarkar D, Patil K, Pandey R, Dasgupta S, Jadhav J, et al. Non-IgA mesangioproliferative glomerulonephritis: a benign entity? Nephrol Dial Transplant. 2012;27(6):2322-7.
34. 34. Usha, Kumar S, Singh RG, Tapas S, Prakash J, Garbyal RS. Mesangioproliferative glomerulonephritis: an important glomerulonephritis in nephrotic syndrome of young adult. Indian J Pathol Microbiol. 2008;51(3):337-41.
35. 35. Thipsawat S. Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature. Diab Vasc Dis Res. 2021;18(6):14791641211058856.
36. 36. Qi C, Mao X, Zhang Z, Wu H. Classification and Differential Diagnosis of Diabetic Nephropathy. J Diabetes Res. 2017;2017:8637138.
37. 37. Lancieri M, Bustaffa M, Palmeri S, Prigione I, Penco F, Papa R, et al. An Update on Familial Mediterranean Fever. Int J Mol Sci. 2023;24(11):9584.
38. 38. Bathobakae L, Ansari N, Mahmoud A, Hasan S, Yuridullah R, Qayyum S, et al. Gastric, Colonic, and Rectal Amyloidosis in the Setting of Familial Mediterranean Fever: A Unique Cause of Intractable Diarrhea. Case Rep Gastrointest Med. 2024;2024:6679725.
39. 39. Kiriakidou M, Ching CL. Systemic Lupus Erythematosus. Ann Intern Med. 2020;172(11):ITC81-ITC96.
40. 40. Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7.