Abstract Objective Angiotensin-converting enzyme 2 (ACE2) gene polymorphisms have been shown to be implicated in hypertension, diabetic nephropathy, and other diseases. However, it remains unclear whether ACE2 gene polymorphisms are involved in the development of primary nephrotic syndrome (PNS) in children. The aim of this study was to assess the association between A9570G polymorphisms of ACE2 gene and PNS in a group of Han children in Guangdong Province, China. Methods The genotype distribution and allele frequency of ACE2 gene A9570G in 66 children with PNS and 60 healthy subjects (control group) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Results Allele frequency and genotype distribution showed no significant difference between the PNS and control groups whether in female or in male children (P>0.05). The PNS group was classified into the glucocorticoid-sensitive and glucocorticoid-resistant subgroups according to glucocorticoid treatment response. Subgroup analysis revealed that in female children, the frequency of GG genotype was 17% in the glucocorticoidsensitive group vs 45% in the glucocorticoid-sensitive group (P=0.018); the frequency of G allele was 31% in the glucocorticoid-sensitive group vs 61% in the glucocorticoid-resistant group (P=0.023). In male children, the frequency of G genotype/G allele was 36% in the glucocorticoid-sensitive group vs 64% in the glucocorticoid-resistant group (P=0.017). Conclusions There is no clear association between ACE2 gene A9570G polymorphisms and childhood PNS, but ACE2 gene A9570G polymorphisms might be associated with glucocorticoid treatment response in children with PNS. The G allele might be a genetic susceptibility factor of glucocorticoid resistance in children with PNS.
Tikellis C, Bernardi S, Burns WC. Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal disease[J]. Curr Opin Nephrol Hypertens, 2011, 20(1): 62-68.
[2]
Burns WC, Thomas MC. Angiotensin II and its role in tubular epithelial to mesenchymal transition associated with chronic kidney disease[J]. Cells Tissues Organs, 2011, 193(1-2): 74-84.
[3]
Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensinconverting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9[J]. Circ Res, 2000, 87(5): E1-E9.
[4]
Prasun P, Prasad N, Tripathi G, et al. Association of angiotensinconverting enzyme gene I/D polymorphism with steroid responsiveness in childhood nephrotic syndrome[J]. Indian J Nephrol, 2011, 21(1): 26-29.
Shiota A, Yamamoto K, Ohishi M, et al. Loss of ACE2 accelerates time-dependent glomerular and tubul ointerstitial damage in streptozotocin-induced diabetic mice[J]. Hypertens Res, 2010, 33 (4): 298-307.
[7]
Nadarajah R, Milagres R, Dilauro M, et al. Podocyte-specific over expression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice[J]. Kidney Int, 2012, 82(3): 292-303.
Eräranta A, Riutta A, Fan M, et al. Dietary phosphate binding and loading alter kidney angiotensin-converting enzyme mRNA and protein content in 5/6 nephrectomized rats[J]. Am J Nephrol, 2012, 35(5): 401-408.
[10]
Loudianos G, Iovicu M, Dessi V, et al. Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B[J]. Hum mutat, 2002, 20(4): 260-266.
[11]
Patnaik M1, Pati P, Swain SN, et al. Association of angiotensinconverting enzyme and angiotensin-converting enzyme-2 gene polymorphisms with essential hypertension in the population of Odisha, India[J]. Ann Hum Biol, 2014, 41(2): 143-150.
[12]
Vašků A, Bienertová-Vašků J, Pařenica J, et al. ACE2 gene polymorphisms and invasively measured central pulse pressure in cardiac patients indicated for coronarography[J]. J Renin Angiotensin Aldosterone Syst, 2013, 14(3): 220-226.
[13]
Chaoxin J, Daili S, Yanxin H, et al. The influence of angiotensinconverting enzyme 2 gene polymorphisms on type 2 diabetes mellitus and coronary heart disease[J]. Eur Rev Med Pharmacol, 2013, 17(19): 2654-2659.
[14]
Currie D, McKnight AJ, Patterson CC, et al. Investigation of ACE, ACE2 and AGTR1 genes for association with nephropathy in Type 1 diabetes mellitus[J]. Diabet Med, 2010, 27(10): 1188- 1194.
[15]
Liu BC, Gao J, Li Q, et al. Albumin caused the increasing production of angiotensin II due to the dysregulation of ACE/ACE2 expression in HK2 cells[J]. Clin Chim Acta, 2009, 403(1-2): 23-30.
