Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

Aravind Selvin Kumar Ramanathan, Balakrishnan Karuppiah, Murali Vijayan, Kamaraj Raju, Dhivakar Mani, Rathika Chinniah, Manikandan Thirunavukkarasu, Padma Malini Ravi, Jeyaram Illiayaraja Krishnan, Prabha Senguttuvan

PDF(166 KB)
PDF(166 KB)
Journal of Biomedical Research ›› 2019, Vol. 33 ›› Issue (3) : 201-207. DOI: 10.7555/JBR.32.20150095
Original Article
Original Article

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

Author information +
History +

Abstract

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%–15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n=51; focal segmental glomerulosclerosis, n=27; diffuse mesangial proliferation, n=8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE‘D’ allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the ‘I’ allele was assessed as having very weak association in cases of minimal change disease. ‘II’ genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of ‘ID’ genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.

Keywords

angiotensin converting enzyme / focal segmental glomerulosclerosis / minimal change disease / nephrotic syndrome

Cite this article

Download citation ▾
Aravind Selvin Kumar Ramanathan, Balakrishnan Karuppiah, Murali Vijayan, Kamaraj Raju, Dhivakar Mani, Rathika Chinniah, Manikandan Thirunavukkarasu, Padma Malini Ravi, Jeyaram Illiayaraja Krishnan, Prabha Senguttuvan. Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome. Journal of Biomedical Research, 2019, 33(3): 201‒207 https://doi.org/10.7555/JBR.32.20150095

References

[1]
Srivastava T, Simon SD, Alon US. High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood[J]. Pediatr Nephrol, 1999, 13(1): 13–18
Pubmed
[2]
Hogg R, Middleton J, Vehaskari VM. Focal segmental glomerulosclerosis--epidemiology aspects in children and adults[J]. Pediatr Nephrol, 2007, 22(2): 183–186
Pubmed
[3]
Hogg RJ, Portman RJ, Milliner D, Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE)[J]. Pediatrics, 2000, 105(6): 1242–1249
Pubmed
[4]
Sharples PM, Poulton J, White RH. Steroid responsive nephrotic syndrome is more common in Asians[J]. Arch Dis Child, 1985, 60(11): 1014–1017
Pubmed
[5]
McKinney PA, Feltbower RG, Brocklebank JT, Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK[J]. Pediatr Nephrol, 2001, 16(12): 1040–1044
Pubmed
[6]
Li RM, Branton MH, Tanawattanacharoen S, Molecular identification of SV40 infection in human subjects and possible association with kidney disease[J]. J Am Soc Nephrol, 2002, 13(9): 2320–2330
Pubmed
[7]
Huang HD, Lin FJ, Li XJ, Genetic polymorphisms of the renin-angiotensin-aldosterone system in Chinese patients with end-stage renal disease secondary to IgA nephropathy[J]. Chin Med J (Engl), 2010, 123(22): 3238–3242
Pubmed
[8]
Kopkan L, Cervenka L. Renal interactions of renin-angiotensin system, nitric oxide and superoxide anion: implications in the pathophysiology of salt-sensitivity and hypertension[J]. Physiol Res, 2009, 58(S2): S55–S67
Pubmed
[9]
Parsa A, Peden E, Lum RF, Association of angiotensin-converting enzyme polymorphisms with systemic lupus erythematosus and nephritis: analysis of 644 SLE families[J]. Genes Immun, 2002, 3(S1): S42–S46
Pubmed
[10]
Uemura K, Nakura J, Kohara K, Association of ACE I/D polymorphism with cardiovascular risk factors[J]. Hum Genet, 2000, 107(3): 239–242
Pubmed
[11]
Lin C, Yang HY, Wu CC, Angiotensin converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension—a meta-regression analysis of 98 observational studies[J]. PLoS One, 2014, 9(1): e87604.
[12]
Naresh VV, Reddy AL, Sivaramakrishna G, Angiotensin converting enzyme gene polymorphism in type II diabetics with nephropathy[J]. Indian J Nephrol, 2009, 19(4): 145–148
Pubmed
[13]
Takezako T, Zhang B, Serikawa T, The D allele of the angiotensin-converting enzyme gene and reperfusion-induced ventricular arrhythmias in patients with acute myocardial infarction[J]. Jpn Circ J, 2001, 65(7): 603–609
Pubmed
[14]
Taniguchi I, Yamazaki T, Wagatsuma K, The DD genotype of angiotensin converting enzyme polymorphism is a risk factor for coronary artery disease and coronary stent restenosis in Japanese patients[J]. Jpn Circ J, 2001, 65(10): 897–900
Pubmed
[15]
Prasun P, Prasad N, Tripathi G, Association of angiotensin-converting enzyme gene I/D polymorphism with steroid responsiveness in childhood nephrotic syndrome[J]. Indian J Nephrol, 2011, 21(1): 26–29
Pubmed
[16]
Oktem F, Sirin A, Bilge I, ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome[J]. Pediatr Nephrol, 2004, 19(4): 384–389
Pubmed
[17]
Patil SJ, Gulati S, Khan F, Angiotensin converting enzyme gene polymorphism in Indian children with steroid sensitive nephrotic syndrome[J]. Indian J Med Sci, 2005, 59(10): 431–435
Pubmed
[18]
Jayapalan JJ. Muniandy S, Chan SP. Null association betweenACE gene I/D polymorphism and diabetic nephropathy among multiethnic Malaysian subjects[J]. Indian J Hum Genet, 2008, 16(2): 78–86.
[19]
Tsai IJ, Yang YH, Lin YH, Angiotensin-converting enzyme gene polymorphism in children with idiopathic nephrotic syndrome[J]. Am J Nephrol, 2006, 26(2): 157–162
Pubmed
[20]
Fahmy ME, Fattouh AM, Hegazy RA, ACE gene polymorphism in Egyptian children with idiopathic nephrotic syndrome[J]. Bratisl Lek Listy, 2008, 109(7): 298–301
Pubmed
[21]
Al-Eisa A, Haider MZ, Srivastva BS. Angiotensin converting enzyme gene insertion/deletion polymorphism in idiopathic nephrotic syndrome in Kuwaiti Arab children[J]. Scand J Urol Nephrol, 2001, 35(3): 239–242
Pubmed
[22]
Saber-Ayad M, Sabry S, Abdel-Latif I, Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism on steroid resistance in Egyptian children with idiopathic nephrotic syndrome[J]. J Renin Angiotensin Aldosterone Syst, 2010, 11(2): 111–118
Pubmed
[23]
Ghorbani A, Omidvar B, Beladi-Mousavi SS, The effect of pentoxifylline on reduction of proteinuria among patients with type 2 diabetes under blockade of angiotensin system: a double blind and randomized clinical trial[J]. Nefrologia, 2012, 32(6): 790–796
Pubmed
[24]
Hohenfellner K, Wingen AM, Nauroth O, Impact of ACE I/D gene polymorphism on congenital renal malformations[J]. Pediatr Nephrol, 2001, 16(4): 356–361
Pubmed
[25]
Sasse B, Hailemariam S, Wüthrich RP, Angiotensin converting enzyme gene polymorphisms do not predict the course of idiopathic nephrotic syndrome in Swiss children[J]. Nephrology (Carlton), 2006, 11(6): 538–541
Pubmed
[26]
Tabel Y, Berdeli A, Mir S, Effects of genetic polymorphisms of the renin-angiotensin system in children with nephrotic syndrome[J]. J Renin Angiotensin Aldosterone Syst, 2005, 6(3): 138–144
Pubmed
[27]
Celik US, Noyan A, Bayazit AK, ACE gene polymorphism in Turkish children with nephrotic syndrome[J]. Ren Fail, 2006, 28(5): 401–403
Pubmed
[28]
Shahid S, Abid A, Mehdi SQ, Association of the ACE-II genotype with the risk of nephrotic syndrome in Pakistani children[J]. Gene, 2012, 493(1): 165–168
Pubmed
[29]
Serdaroglu E, Mir S, Berdeli A, ACE gene insertion/deletion polymorphism in childhood idiopathic nephrotic syndrome[J]. Pediatr Nephrol, 2005, 20(12): 1738–1743
Pubmed
[30]
Reiser J, von Gersdorff G, Loos M, Induction of B7-1 in podocytes is associated with nephrotic syndrome[J]. J Clin Invest, 2004, 113(10): 1390–1397
Pubmed
[31]
Luther Y, Bantis C, Ivens K, Effects of the genetic polymorphisms of the renin-angiotensin system on focal segmental glomerulosclerosis[J]. Kidney Blood Press Res, 2003, 26(5–6): 333–337
Pubmed
[32]
Hartleben B, Gödel M, Meyer-Schwesinger C, Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice[J]. J Clin Invest, 2010, 120(4): 1084–1096
Pubmed
[33]
Qiu MY, Xie QF, Wang LN, Association between angiotensin-converting enzyme 2 gene polymorphisms and childhood primary nephrotic syndrome[J]. Zhongguo Dang Dai Er Ke Za Zhi, 2015, 17(3): 232–236
Pubmed
[34]
Sasongko TH, Sadewa AH, Kusuma PA, ACE gene polymorphism in children with nephrotic syndrome in the Indonesian population[J]. Kobe J Med Sci, 2005, 51(3–4): 41–47
Pubmed
[35]
Zhou TB, Qin YH, Su LN, Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and susceptibility of minimal change nephrotic syndrome: a meta-analysis[J]. Int J Nephrol, 2011, 2011: 360357.
[36]
Yuan M, Duan Z, Sun Y, Effects of estrogen on ACE-Ang II-AT1 axis in ovariectomy and hypoxic pulmonary hypertension rats[J]. Zhonghua Yi Xue Za Zhi, 2014, 94(22): 1696–1700
Pubmed
[37]
Higaki J, Baba S, Katsuya T, Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men: the suita study[J]. Circulation, 2000, 101(17): 2060–2065
Pubmed

Acknowledgments

This work was supported by Networking Resource Centre in Biological Sciences (NRCBS; funded by UGC, Govt. of India). The author (RASK) thank the Co-ordinator, UGC-NRCBS, Madurai Kamaraj University, for providing the MKU-NRCBS visiting fellowship.

RIGHTS & PERMISSIONS

2018 2018 by the Journal of Biomedical Research.
PDF(166 KB)

Accesses

Citations

Detail

Sections
Recommended

/