ABSTRACT
Idiopathic nephrotic syndrome [INS] is one of the common renal disorders in childhood. Dyslipidemia is not only an important manifestation of INS, but is also involved in cardiovascular diseases and in progressive glomerular damage leading to renal failure. Apolipoprotein E [apo E] has been identified as an important candidate gene for lipid metabolism abnormalities. In the kidney, apo E gene mutation may play a role in aggravating the glomerular basement membrane lesion and promoting proteinuria. Our objective is to investigate the association of apo E serum level and genetic polymorphism [E[2], E[3], and E[4]] with responsiveness to steroid treatment as well as renal pathology in children with INS. Design: Case-control study. One study center at Center of Pediatric Nephrology and Transplantation [CPNT], Cairo University Children's Hospital. Forty seven pediatric patients with INS and 11 age and sex-matched controls were enrolled in the study, Twenty two of the patients had steroid-sensitive nephrotic syndrome [SSNS] and 25 had steroid-resistant nephrotic syndrome [SRNS]. Genomic DNA was extracted from children with INS and controls, and ape E genotype was determined by Real time-PCR analysis. The serum ape E, total cholesterol [TC], albumin, creatinine, and urine protein to creatinine ratio [UP/UCr] were also measured in both groups. Serum ape E was significantly higher in SRNS than SSNS [p=0.01] and controls [p=0.03]. Serum total cholesterol [TC] was significantly higher in SRNS than controls [p=0.028]. Significant positive correlation was found between serum apo E and UP/UCr [r=0.327, p=0.03]. Apo E[4] allele was only found in NS [8.5%] and absent in the control group. Apo E genotype E4E4 was found in one patient only in SRNS group with pathology of Focal segmental glomeruloscierosis [FSGS] while it was absent in SSNS and control groups, but this was not statistically significant. Heterozygous E[3]E[4] was only present in MS groups and not in control group [12% In SRNS and 13.64% in SSNS]. E[2]E[2] genotype was also found only in SRNS [4%] with the pathology of FSGS, which was not significant but the allelic frequency of E[2] was significantly higher in SRNS than SSNS [P=0.036]. E[3]E[3] was the most common genotype in the 3 groups and the allelic E[3] presentation was statistically higher in SSNS than in SRNS [P=0.04] The high frequency of E[4] only in nephrotic children and not in controls suggests that E[4] may share, as a genetic marker, in predisposition to childhood INS. The higher frequency of the E[2] allele in SRNS patients suggests that the E[2] allele gives a possible genetic predilection to steroid resistance in our population while the significantly higher E[3] in SSNS group may convey a readiness to steroid responsiveness related to E3, but further studies are needed to clarify this subject