SNPs at 3′UTR of APOL1 and miR-6741-3p target sites associated with kidney diseases more susceptible to SARS-COV-2 infection: in silco and in vitro studies
Acute Kidney Injury (AKI) is a common manifestation of COVID-19 and several cases have been reported in the setting of the high-risk APOL1 genotype (common genetic variants). This increases the likelihood that African American people with the high-risk genotype APOL1 are at increased risk for kidney...
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Published in | Mammalian genome Vol. 32; no. 5; pp. 389 - 400 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.10.2021
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Acute Kidney Injury (AKI) is a common manifestation of COVID-19 and several cases have been reported in the setting of the high-risk APOL1 genotype (common genetic variants). This increases the likelihood that African American people with the high-risk genotype
APOL1
are at increased risk for kidney disease in the COVID-19 environment. Single-nucleotide polymorphisms (SNPs) are found in various microRNAs (miRNAs) and target genes change the miRNA activity that leads to different diseases. Evidence has shown that SNPs increase/decrease the effectiveness of the interaction between miRNAs and disease-related target genes. The aim of this study is not only to identify miRSNPs on the
APOL1
gene and SNPs in miRNA genes targeting 3′UTR but also to evaluate the effect of these gene variations in kidney patients and their association with SARS-COV-2 infection. In 3′UTR of the
APOL1
gene, we detected 96 miRNA binding sites and 35 different SNPs with 10 different online software in the binding sites of the miRNA (in silico). Also we studied gene expression of patients and control samples by using qRT-PCR (in vitro). In silico study, the binding site of miR-6741-3p on
APOL1
has two SNPs (rs1288875001, G > C; rs1452517383, A > C) on
APOL1
3′UTR, and its genomic sequence is the same nucleotide as rs1288875001. Similarly, two other SNPs (rs1142591, T > A; rs376326225, G > A) were identified in the binding sites of miR-6741-3p at the first position. Here, the miRSNP (rs1288875001) in APOL1 3′UTR and SNP (rs376326225) in the miR-6741-3p genomic sequence are cross-matched in the same binding region. In vitro study, the relative expression levels were calculated by the 2
−ΔΔCt
method & Mann–Whitney
U
test. The expression of
APOL1
gene was different in chronic kidney patients along with COVID-19. By these results,
APOL1
expression was found lower in patients than healthy (
p
< 0.05) in kidney patients along with COVID-19. In addition, miR-6741-3p targets many
APOL1
-related genes (
TLR7, SLC6A19, IL-6,10,18, chemokine (C–C motif) ligand 5, SWT1, NFYB, BRF1, HES2, NFYB, MED12L, MAFG, GTF2H5, TRAF3, angiotensin II receptor-associated protein, PRSS23
) by evaluating online software in the binding sites of the miR-6741-3p. miR-6741-3p has not previously shown any association with kidney diseases and SARS-COV-2 infection. It assures that
APOL1
can have a significant consequence in kidney-associated diseases by different pathways. Henceforth, this study represents and demonstrates an effective association between miR-6741-3p and kidney diseases, i.e., collapsing glomerulopathy, chronic kidney disease (CKD), acute kidney injury (AKI), and tubulointerstitial lesions susceptibility to SARS-COV-2 infection via in silico and in vitro exploration and recommended to have better insight. |
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ISSN: | 0938-8990 1432-1777 |
DOI: | 10.1007/s00335-021-09880-6 |