ACE Gene Insertion/deletion Polymorphism in Childhood Idiopathic Nephrotic Syndrome

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2005 Oct 7

PMID 16208534

Citations 8

Authors

Erkin Serdaroglu

Sevgi Mir

Afig Berdeli

Nejat Aksu

Mustafa Bak

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to determine the distribution of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its effects on clinical, laboratory, histological findings, treatment responses and progression to end-stage renal disease in childhood idiopathic nephrotic syndrome (NS). 227 children diagnosed with idiopathic NS were included in the study. Eighty-three of patients were steroid resistant and 77 of patients were focal segmental glomerulosclerosis. The control group was consisted of 287 unrelated healthy adult volunteers. ACE gene I/D polymorphism were analyzed by using PCR based method. In the entire group of children with NS, the frequencies of the II, ID, and DD genotypes of ACE gene were 13.7%, 38.3% and 48%, respectively. D allele frequency was higher in NS group than control group (0.67 vs. 0.56, p=0.001). Percentage of frequent relapser patients was found more frequently in ID or DD genotype (38.7%) than II genotype (15%) when only steroid sensitive patients were evaluated (p=0.045). The D-allele frequency was 0.65, 0.69 and 0.68 respectively in focal segmental glomerulosclerosis, biopsy proven minimal change and entire minimal change group (p>0.05) and 0.69 and 0.64 respectively in steroid sensitive and resistant groups (p>0.05). D allele frequency was not significantly different in patients with or without end-stage renal disease (0.64 vs. 0.67 respectively, p>0.005) when 115 patients who were at least five year follow-up were evaluated. The D allele frequency was higher in NS patients than healthy controls and DD or ID genotype was related with frequent relapses. ACE gene I/D polymorphism was not important in laboratory and histological findings and progression of the disease in children with NS.

Citing Articles

SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype.

Yamamoto N, Ariumi Y, Nishida N, Yamamoto R, Bauer G, Gojobori T Gene. 2020; 758:144944.

PMID: 32628976 PMC: 7833925. DOI: 10.1016/j.gene.2020.144944.

Genetics of Childhood Steroid Sensitive Nephrotic Syndrome: An Update.

Lane B, Cason R, Esezobor C, Gbadegesin R Front Pediatr. 2019; 7:8.

PMID: 30761277 PMC: 6361778. DOI: 10.3389/fped.2019.00008.

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

Kumar Ramanathan A, Karuppiah B, Vijayan M, Raju K, Mani D, Chinniah R J Biomed Res. 2018; 33(3):201-207.

PMID: 30333281 PMC: 6551426. DOI: 10.7555/JBR.32.20150095.

Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphism and Susceptibility of Minimal Change Nephrotic Syndrome: A Meta-Analysis.

Zhou T, Qin Y, Su L, Lei F, Huang W, Zhao Y Int J Nephrol. 2011; 2011:360357.

PMID: 21660286 PMC: 3106969. DOI: 10.4061/2011/360357.

Association of angiotensin-converting enzyme gene I/D polymorphism with steroid responsiveness in childhood nephrotic syndrome.

Prasun P, Prasad N, Tripathi G, Jafar T, Sharda S, Gulati S Indian J Nephrol. 2011; 21(1):26-9.

PMID: 21655166 PMC: 3109779. DOI: 10.4103/0971-4065.75215.

References

Antignac C . Genetic models: clues for understanding the pathogenesis of idiopathic nephrotic syndrome. J Clin Invest. 2002; 109(4):447-9. PMC: 150884. DOI: 10.1172/JCI15094. View

Samani N, Thompson J, OToole L, Channer K, Woods K . A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation. 1996; 94(4):708-12. DOI: 10.1161/01.cir.94.4.708. View

. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension.... Pediatrics. 1996; 98(4 Pt 1):649-58. View

Hori C, Hiraoka M, Yoshikawa N, Tsuzuki K, Yoshida Y, Yoshioka K . Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis. Nephron. 2001; 88(4):313-9. DOI: 10.1159/000046014. View

Baboolal K, Ravine D, Daniels J, Williams N, Holmans P, Coles G . Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease. Kidney Int. 1997; 52(3):607-13. DOI: 10.1038/ki.1997.373. View

Ruiz-Ortega M, Lorenzo O, Suzuki Y, Ruperez M, Egido J . Proinflammatory actions of angiotensins. Curr Opin Nephrol Hypertens. 2001; 10(3):321-9. DOI: 10.1097/00041552-200105000-00005. View

Nakamura S, Nakamura I, Ma L, Vaughan D, Fogo A . Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo. Kidney Int. 2000; 58(1):251-9. DOI: 10.1046/j.1523-1755.2000.00160.x. View

Ruiz-Ortega M, Lorenzo O, Ruperez M, Konig S, Wittig B, Egido J . Angiotensin II activates nuclear transcription factor kappaB through AT(1) and AT(2) in vascular smooth muscle cells: molecular mechanisms. Circ Res. 2000; 86(12):1266-72. DOI: 10.1161/01.res.86.12.1266. View

Luther Y, Bantis C, Ivens K, Fehsel K, Kolb-Bachhofen V, Heering P . Effects of the genetic polymorphisms of the renin-angiotensin system on focal segmental glomerulosclerosis. Kidney Blood Press Res. 2003; 26(5-6):333-7. DOI: 10.1159/000073939. View

10.

Frishberg Y, Becker-Cohen R, Halle D, Feigin E, Eisenstein B, Halevy R . Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children. Kidney Int. 1998; 54(6):1843-9. DOI: 10.1046/j.1523-1755.1998.00218.x. View

11.

Hohenfellner K, Hunley T, Brezinska R, Brodhag P, Shyr Y, Brenner W . ACE I/D gene polymorphism predicts renal damage in congenital uropathies. Pediatr Nephrol. 1999; 13(6):514-8. DOI: 10.1007/s004670050649. View

12.

Stratta P, Canavese C, Ciccone G, Barolo S, DallOmo A, Fasano M . Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an italian population. Am J Kidney Dis. 1999; 33(6):1071-9. DOI: 10.1016/S0272-6386(99)70144-7. View

13.

Al-Eisa A, Haider M, Srivastva B . Angiotensin converting enzyme gene insertion/deletion polymorphism in idiopathic nephrotic syndrome in Kuwaiti Arab children. Scand J Urol Nephrol. 2001; 35(3):239-42. DOI: 10.1080/003655901750292033. View

14.

Lee D, Kim W, Kang S, Koh G, Park S . Angiotensin-converting enzyme gene polymorphism in patients with minimal-change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron. 1997; 77(4):471-3. DOI: 10.1159/000190326. View

15.

Cambien F, Poirier O, Lecerf L, Evans A, Cambou J, Arveiler D . Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992; 359(6396):641-4. DOI: 10.1038/359641a0. View

16.

Fujisawa T, Ikegami H, Kawaguchi Y, Hamada Y, Ueda H, Shintani M . Meta-analysis of association of insertion/deletion polymorphism of angiotensin I-converting enzyme gene with diabetic nephropathy and retinopathy. Diabetologia. 1998; 41(1):47-53. DOI: 10.1007/s001250050865. View

17.

Mezzano S, Ruiz-Ortega M, Egido J . Angiotensin II and renal fibrosis. Hypertension. 2001; 38(3 Pt 2):635-8. DOI: 10.1161/hy09t1.094234. View

18.

COSTEROUSSE O, Allegrini J, Lopez M, Alhenc-Gelas F . Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J. 1993; 290 ( Pt 1):33-40. PMC: 1132379. DOI: 10.1042/bj2900033. View

19.

Schwartz G, Brion L, Spitzer A . The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987; 34(3):571-90. DOI: 10.1016/s0031-3955(16)36251-4. View

20.

Oktem F, Sirin A, Bilge I, Emre S, Agachan B, Ispir T . ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2004; 19(4):384-9. DOI: 10.1007/s00467-003-1398-4. View