Correlation Between Single-Nucleotide Polymorphisms Within miR-30a and Related Target Genes and Risk or Prognosis of Nephrotic Syndrome

Abstract

This study was aimed to figure out the association of single-nucleotide polymorphisms (SNPs) within miR-30a and its downstream molecules (i.e., Notch1, Snail1, p53, CD73, and TET1) with susceptibility to and prognosis of nephrotic syndrome (NS). In the aggregate, 265 patients and 281 healthy controls were gathered, and related laboratory indicators were examined. The miR-30a, Notch1, Snail1, TET1, p53, and CD73 expressions were also evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, or enzyme-linked immunosorbent assay. Besides, the SNPs were genotyped by RT-PCR with aid of ABI-PRISM^™ 377 DNA sequencing instrument. As a result, the NS patients were correlated with remarkably higher 24-h protein excretion, random urine protein/creatinine (UPCR), and serum creatinine, along with lower estimated glomerular filtration rate and serum albumin, when compared with normal subjects (p < 0.05). Furthermore, significant correlations were present between miR-30a expression and the expressions of Notch1 (r_s = -0.350), p53 (r_s = -0.339), CD73 (r_s = -0.300), TET1 (r_s = -0.249), and Snail1 (r_s = -0.829) (all p < 0.05). The SNPs of miR-30a [i.e., rs2222722 (C>T)], Notch1 [i.e., rs3124599 (G>A), rs3124591 (C>T), and rs139994842 (G>A)], Snail1 [i.e., rs6020178 (T>C)], p53 [i.e., rs1042522 (C>G)], and CD73 [i.e., rs9444348 (G>A) and rs4431401 (T>C)] were significantly correlated with both differed NS risk and altered hormone sensitivity to NS (all p < 0.05). Moreover, haplotype AC of CD73 and haplotype ATG of Notch1 were the helpful factors against NS (p < 0.05), yet haplotype GT of CD73 functioned oppositely (p < 0.05). The haplotype AT of CD73 was beneficial to the NS patients for that the carriers could be treated with hormones without severe complications (p < 0.05). Conclusively, the SNPs situated within miR-30a and its downstream molecules (i.e., Notch1, Snail1, p53, CD73, and TET1) could become the promising biomarkers for both NS diagnosis and prediction of NS prognosis.

Keywords: CD73; Notch1; Snail1; TET1; miR-30a; nephrotic syndrome; p53; single-nucleotide polymorphisms.