MEMBRANÖZ NEFROPATİLİ HASTALARDA PLA2R1 POLİMORFİZMİNİN ETKİSİNİN ARAŞTIRILMASI

Abstract

Amaç: Membranöz nefropati (MN), erişkinlerde nefrotik sendromun en sık nedenidir. Fosfolipaz A2 reseptörü (PLA2R1), mannoz reseptör ailesine (~180 kDa) ait glikoproteindir. PLA2R1, idiyopatik MN patogenezi ile ilişkili bulunmuş, PLA2R1 antikorlarının varlığının hastalıkla ilişkisi desteklenmiştir. Bu çalışmada PLA2R1 rs35771982’nin Membranöz Nefropati ile ilişkisi araştırıldı. Gereç ve Yöntemler: Çalışmaya MN tanısı alan 88 hasta ve bu hastalarla ilişkisi olmayan 101 sağlıklı birey dahil edildi. Hasta ve kontrol gruplarının PLA2R1 rs35771982’si Real Time PCR (Polimeraz Zincir Reaksiyonu) yöntemi ile incelendi. Bulgular: Hastaları sağlıklı kontrollerle karşılaştırdığımızda rs35771982 GG genotipinin hastalarda anlamlı derecede yüksek olduğu görüldü. Türk popülasyonunda rs35771982 CG genotipinin yaygın olduğu bulundu. Sonuç: PLA2R1 rs35771982 GG genotipinin MN’ye duyarlılıkla ilişkili olduğu bulundu.

Keywords

• Membranöz nefropati
• PLA2R1
• rs35771982
• Gerçek zamanlı PZR

INVESTIGATION OF THE EFFECT OF PLA2R1 POLYMORPHISM IN PATIENTS WITH MEMBRANOUS NEPHROPATHY

Abstract

Objective: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Phospholipase A2 receptor (PLA2R1) is a glycoprotein belonging to the mannose receptor family (~180 kDa). PLA2R1 was found to be associated with idiopathic MN pathogenesis, and the presence of PLA2R1 antibodies was supported by the diseases. In this study, the association of PLA2R1 rs35771982 with membranous nephropathy was investigated. Material and Methods: The study included 88 patients diagnosed with MN and 101 healthy individuals unrelated to the patients. The PLA2R1 rs35771982 levels of the patient and control groups were examined using the Real Time PCR (Polymerase Chain Reaction) method. Results: The comparison of the patients with healthy controls in this study showed that the rs35771982 GG genotype was significantly higher in the patients. The genotype of rs35771982 in the Turkish population was found to be common to the CG genotype. Conclusion: Our findings revealed that the PLA2R1 rs35771982 GG genotype is associated with susceptibility to MN.

Keywords

• Membranous nephropathy
• PLA2R1
• rs35771982
• Real-time PCR

References

1. 1. Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, et al. Risk HLA-DQA1 and PLA2R1 alleles in idiopathic membranous nephropathy. N Engl J Med 2011;364(7):616-26. google scholar
2. 2. Lai WL, Yeh TH, Chen PM, Chan CK, Chiang WC, Chen YM, et al. Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment. J Formos Med Assoc 2015;114(2):102-11. google scholar
3. 3. Beck LHJr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009;361(1):11-21. google scholar
4. 4. Ancian P, Lambeau G, Mattei MG, Lazdunski M. The Human 180-kDa Receptor for Secretory Phospholipases a2 molecular clonıng, ıdentıfıcatıon of a secreted soluble form, expressıon, and chromosomal localızatıon. J Biol Chem 1995;270(15):8963-70. google scholar
5. 5. Saeed M, Beggs ML, Walker PD, Larsen CP. PLA2R-associated membranous glomerulopathy is modulated by common variants in PLA2R1 and HLA-DQA1 genes. Genes Immun 2014;15(8):556-61. google scholar
6. 6. Kim S, Chin HJ, Na KY, Kim S, Oh J, Chung W, et al. Single nucleotide polymorphisms in the phospholipase A2 receptor gene are associated with genetic susceptibility to idiopathic membranous nephropathy. Nephron Clin Pract 2011;117(3):c253-8. google scholar
7. 7. Liu YH, Chen CH, Chen SY, Lin YJ, Liao WL, Tsai CH, et al. Association of phospholipase A2 receptor 1 polymorphism with idiopathic membranous nephropathy in Chinese patients in Taiwan. J Biomed Sci 2010;17(1):81. google scholar
8. 8. Coenen MJ, Hofstra JM, Debiec H, Stanescu HC, Medlar AJ, Stengel B, et al. Phospholipase A2 receptor (PLA2R1) sequence variants in idiopathic membranous nephropathy. J Am Soc of Nephrol 2013;24(4):677-83. google scholar

9. 9. Lv J, Hou W, Zhou X, Liu G, Zhou F, Zhao N, et al. Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy. J Am Soc Nephrol 2013;24(8):1323-9. google scholar
10. 10. Ramachandran R, Kumar V, Kumar A, Yadav AK, Nada R, Kumar H, et al. PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians. Nephrol Dial Transplant 2016;31(9):1486-93. google scholar
11. 11. Wang F, Wang TT, Liang XW, Lu JD, Xie QH, Chen RY, et al. PLA2R1 and HLA-DQA1 gene variations in idiopathic membranous nephropathy in South China. Ann Acad Med Singap 2021;50(1):33-41. google scholar
12. 12. Tian CX, Li L, Qiu P, Qiu YR. Association of SNPs in PLA2R1 with idiopathic and secondary membranous nephropathy in two Chinese cohorts. Br J Biomed Sci 2020;77(1):24-8. google scholar
13. 13. Zhu H, Han Q, Zhang D, Wang Y, Gao J, Yang X, et al. The clinicopathological features of patients with membranous nephropathy. Int J Nephrol Renovasc Dis 2018;18(11):33-40. google scholar
14. 14. Zhou GY, Liu F, Zhang WL. Association of single nucleotide polymorphism in M-type phospholipase A2 receptor gene with membranous nephropathy. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2013;30(6):706-10. google scholar
15. 15. Liu X, Xu W, Yu C, Wang M, Liu R, Xie, R. Associations between m-type phospholipase A2 receptor, human leukocyte antigen gene polymorphisms and idiopathic membranous nephropathy. Bioengineered 2021;12(1):8833-8844. google scholar
16. 16. Thiri M, Honda K, Kashiwase K, Mabuchi A, Suzuki H, Watanabe K, et al. High-density association mapping and interaction analysis of PLA2R1 and HLA regions with idiopathic membranous nephropathy in Japanese. Sci Rep 2016;6(1):38189. google scholar
17. 17. Kaga H, Komatsuda A, Omokawa A, Okuyama S, Mori K, Wakui H, et al. Analysis of PLA2R1 and HLA-DQA1 sequence variants in Japanese patients with idiopathic and secondary membranous nephropathy. Clin Exp Nephrol 2018;22(2):275-82. google scholar