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Mutation analysis of TRPC6 gene in nephrotic syndrome in children from a single center

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DOI: 10.23977/medbm.2024.020112 | Downloads: 7 | Views: 107

Author(s)

Junhua Deng 1, Zengpo Huang 1, Sanju Yang 2, Yunguang Liu 1

Affiliation(s)

1 Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
2 Youjiang Medical University for Nationalities, Baise, China

Corresponding Author

Yunguang Liu

ABSTRACT

We analyzed the correlation between two single nucleotide polymorphism sites (rs12366144 and rs7931399) on TRPC6 gene and primary nephrotic syndrome (PNS). 205 cases of Guangxi Zhuang children were selected, of which 108 cases were in the PNS group and 97 cases were in the healthy control group who came to our hospital for physical examination in the same period. The rs12366144 and rs7931399 loci of the TRPC6 gene were genotyped using second-generation genetic testing technology, and their correlation with the development of PNS was analyzed. Logistic regression analysis was used for association analysis. Haplogroup construction was also performed for both loci using SHEsis software to analyze the association between both loci and PNS. The polymorphisms at rs12366144, rs7931399 loci of TRPC6 gene may not be significantly related to the development of primary nephrotic syndrome in Guangxi Zhuang children.

KEYWORDS

PNS, TRPC6, Single Nucleotide Polymorphism, Children

CITE THIS PAPER

Junhua Deng, Zengpo Huang, Sanju Yang, Yunguang Liu, Mutation analysis of TRPC6 gene in nephrotic syndrome in children from a single center. MEDS Basic Medicine (2024) Vol. 2: 94-101. DOI: http://dx.doi.org/10.23977/medbm.2024.020112.

REFERENCES

[1] S-A Politano, Colbert G-B, Hamiduzzaman N. Nephrotic Syndrome[J]. Prim Care, 2020, 47(4): 597-613.
[2] M Nagata. Podocyte injury and its consequences[J]. Kidney Int, 2016, 89(6): 1221-1230.
[3] C-E Sadowski, Lovric S, Ashraf S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome [J]. J Am Soc Nephrol, 2015, 26(6): 1279-1289.
[4] A-S AbuMaziad, Abusaleh R, Bhati S. Congenital nephrotic syndrome[J]. J Perinatol, 2021, 41(12): 2704-2712.
[5] J-K Warejko, Tan W, Daga A, et al. Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome[J]. Clin J Am Soc Nephrol, 2018, 13(1): 53-62.
[6] L-K Farmer, Rollason R, Whitcomb D-J, et al. TRPC6 Binds to and Activates Calpain, Independent of Its Channel Activity, and Regulates Podocyte Cytoskeleton, Cell Adhesion, and Motility[J]. J Am Soc Nephrol, 2019, 30(10): 1910-1924.
[7] National Kidney Foundation .K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification[J]. Am J Kidney Dis, 2002, 39(2 Suppl 1): S1-S266.
[8] B-B Joshi, Koringa P-G, Mistry K-N, et al. In silico analysis of functional nsSNPs in human TRPC6 gene associated with steroid resistant nephrotic syndrome[J]. Gene, 2015, 572(1): 8-16.
[9] M Wang, Wang R, He X, et al. Two Children With Novel TRPC6 Spontaneous Missense Mutations and Atypical Phenotype: A Case Report and Literature Review[J]. Front Pediatr, 2020, 8269.
[10] M-P Winn, Conlon P-J, Lynn K-L, et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis[J]. Science, 2005, 308(5729): 1801-1804.
[11] H Wang, Cheng X, Tian J, et al. TRPC channels: Structure, function, regulation and recent advances in small  molecular probes[J]. Pharmacol Ther, 2020, 209107497.
[12] Q Tang, Guo W, Zheng L, et al. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels[J]. Cell Res, 2018, 28(7): 746-755.
[13] Q Wang, Tian X, Wang Y, et al. Role of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement[J]. J Diabetes Res, 2020, 20206897390.
[14] Y Zhai, Li D, Wang Z, et al. Cortex Mori Radicis Attenuates Streptozotocin-induced Diabetic Renal Injury in Mice via Regulation of Transient Receptor Potential Canonical Channel 6[J]. Endocr Metab Immune Disord Drug Targets, 2022, 22(8): 862-873.
[15] D Spires, Ilatovskaya D-V, Levchenko V, et al. Protective role of Trpc6 knockout in the progression of diabetic kidney disease[J]. Am J Physiol Renal Physiol, 2018, 315(4): F1091-F1097.
[16] E-Y Kim, Yazdizadeh Shotorbani-P, Dryer S-E. Trpc6 inactivation confers protection in a model of severe nephrosis in rats[J]. J Mol Med (Berl), 2018, 96(7): 631-644.
[17] Y Feng, Li M, Wang Y, et al. Activation of TRPC6 by AngⅡ Induces Podocyte Injury and Participates in Proteinuria of Nephrotic Syndrome[J]. Front Pharmacol, 2022, 13915153.
[18] W Tan, Lovric S, Ashraf S, et al. Analysis of 24 genes reveals a monogenic cause in 11.1% of cases with steroid-resistant nephrotic syndrome at a single center[J]. Pediatr Nephrol, 2018, 33(2): 305-314.
[19] H Hanafusa, Hidaka Y, Yamaguchi T, et al. Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis[J]. Am J Med Genet A, 2021, 185(7): 2175-2179.
[20] F Wang, Zhang Y, Mao J, et al. Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome[J]. Pediatr Nephrol, 2017, 32(7): 1181-1192.
[21] D Wang, Li X, Liu J, et al. Effects of TRPC6 on invasibility of low-differentiated prostate cancer cells[J]. Asian Pac J Trop Med, 2014, 7(1): 44-47.
[22] Y Song, Liu G, Liu S, et al. Helicobacter pylori upregulates TRPC6 via Wnt/beta-catenin signaling to promote  gastric cancer migration and invasion[J]. Onco Targets Ther, 2019, 5269-5279.
[23] I Jardin, Diez-Bello R, Falcon D, et al. Melatonin downregulates TRPC6, impairing store-operated calcium entry in triple-negative breast cancer cells[J]. J Biol Chem, 2021, 296100254.
[24] K Gusev, Shalygin A, Kolesnikov D, et al. Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats[J]. Int J Mol Sci, 2023, 24(8):e288.
[25] L Kong, Sun R, Zhou H, et al. Trpc6 knockout improves behavioral dysfunction and reduces Abeta production by inhibiting CN-NFAT1 signaling in T2DM mice[J]. Exp Neurol, 2023, 363114350.
[26] S-F Heeringa, Moller C-C, Du J, et al. A novel TRPC6 mutation that causes childhood FSGS[J]. PLoS One, 2009, 4(11): e7771.
[27] G Hall, Rowell J, Farinelli F, et al. Phosphodiesterase 5 inhibition ameliorates angiontensin II-induced podocyte  dysmotility via the protein kinase G-mediated downregulation of TRPC6 activity[J]. Am J Physiol Renal Physiol, 2014, 306(12): F1442-F1450.
[28] Y Yu, Keller S-H, Remillard C-V, et al. A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension[J]. Circulation, 2009, 119(17): 2313-2322.
[29] Y Wang, Ding M, Chaudhari S, et al. Nuclear factor kappaB mediates suppression of canonical transient receptor potential 6 expression by reactive oxygen species and protein kinase C in kidney cells[J]. J Biol Chem, 2013, 288(18): 12852-12865.
[30] X-Y Kuang, Huang W-Y, Xu H, et al. 254C>G: a TRPC6 promoter variation associated with enhanced transcription and steroid-resistant nephrotic syndrome in Chinese children[J]. Pediatr Res, 2013, 74(5): 511-516.
[31] J-M Hofstra, Coenen M-J, Schijvenaars M-M, et al. TRPC6 single nucleotide polymorphisms and progression of idiopathic membranous nephropathy[J]. PLoS One, 2014, 9(7): e102065.

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