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

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

doi:10.7555/jbr.32.20150095

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.

Highlights

Nephrotic syndrome (NS) is a condition where damages are prominent in filtering units of kidney
We found II genotype frequency was observed in 29.41% (15/51) of the minimal change disease (MCD) cases and in 11.11% (3/ 27) focal segmental glomerulosclerosis (FSGS) cases
The analysis revealed that the degree of dominance was < 1 from the Angiotensin converting enzyme (ACE) (I/D) variant and NS in South Indian children

Summary

Introduction

Nephrotic syndrome (NS) is a condition where damages are prominent in filtering units of kidney. NS is more predominant in children and commonly exists in the ages of 2 and 8 years. It seems to affect boys more often than girls[1–2]. A geographically based epidemiological study of NS suggested that Asian children have higher incidence; mainly, it was higher in lower socioeconomic groups[5–6]. The histological evaluation of renal tissues in nephrotic cases has three main categories: minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and diffuse mesangial proliferation (DMP). MCD is idiopathic, with no change in the number of podocytes and it mostly responds to steroid treatment (remission). FSGS is a severe form which decreases the number of podocytes and does not respond to steroid treatment. DMP is a severe form of nephrotic which is rarely seen

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Conclusion