APOL1-Associated Collapsing Focal Segmental Glomerulosclerosis in a Patient With Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset in Infancy (SAVI).
Apolipoprotein L1 (APOL1) risk variants are strongly associated with sporadic focal segmental glomerulosclerosis (FSGS) in populations with African ancestry.
APOL1-associated primary glomerular diseases include focal segmental glomerulosclerosis, human immunodeficiency virus-associated nephropathies, and arterionephrosclerosis.
This study aims to establish an aetiological link between dengue virus (DENV) infection and the collapsing variant of FSGS and to analyse possible influences of the <i>apolipoprotein 1 (APOL1)</i> gene risk alleles on the disease.
We present a series of cases of presumed de novo collapsing FSGS in 5 transplanted kidneys from 3 deceased donors later identified as carrying 2 APOL1 risk alleles, including 2 recipients from the same donor whose kidneys were transplanted in 2 different institutions.
Some of the most striking findings relate to APOL1 genetic variants, seen exclusively in individuals of sub-Saharan African descent, that create a predisposition to particular renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis.
Discovery of the apolipoprotein L1 gene (APOL1) association with focal segmental glomerulosclerosis, human immunodeficiency virus (HIV)-associated nephropathy, lupus nephritis, sickle cell nephropathy, and solidified glomerulosclerosis, as well as more rapid failure of transplanted kidneys from donors with APOL1 renal-risk genotypes, has improved our understanding of nondiabetic nephropathy.
The major focus of this commentary on providing understanding about the <i>apolipoprotein 1</i> (<i>APOL1</i>) gene, the protein encoded by this gene (apoL1) and the mechanistic details regarding the role of apoL1 in the lysis of <i>Trypanosoma brucei</i> Information about <i>APOL1</i> genetic variants, <i>APOL1G1</i> and <i>APOL1G2</i>, is provided along with the association of these variants with hypertension-attributed end-stage renal disease (ESRD) and focal segmental glomerulosclerosis (FSGS).
Two genetic variants in apolipoprotein L1 (APOL1) are associated with increased risk of focal segmental glomerulosclerosis as well as other glomerular phenotypes.
There was no significant difference in the distribution of APOL1 gene copy variants between FSGS patients and normal controls, and there was no significant correlation between the APOL1 gene CNV and the FSGS patients' clinical manifestations.
APOL1 nephropathies comprise a range of clinical and pathologic syndromes, which can be summarized as focal segmental glomerulosclerosis, in various guises, and arterionephrosclerosis, otherwise known as hypertensive kidney diseases.
Although nephropathies that are associated with variants in the apolipoprotein L1 gene (APOL1) often cause secondarily elevated blood pressure, they belong to the spectrum of focal segmental glomerulosclerosis and are not initiated by systemic hypertension.
The contribution of African ancestry to the risk of focal segmental glomerulosclerosis and chronic kidney disease has been partially explained by the recently described chromosome 22q variants in the gene apolipoprotein L1 (APOL1).
Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility.
We investigated the incidence of APOL1 variants in young African Americans with hypertension or FSGS and a family history of ESRD by conducting a case-control study of 93 pediatric and young adult African Americans with hypertension or FSGS to determine the association with APOL1 risk variants, G1, and G2 using custom-made TaqMan-based allelic discrimination assays.
Thus, only APOL1 G1 and G2 confer renal risk, and other common and rare APOL1 missense variants, including the archaic G3 haplotype, do not contribute to sporadic FSGS and HIVAN in the US population.
An exception appears to be APOL1, which harbors common variants responsible for the high rate of FSGS and other nephropathies in people of recent African ancestry.
The prevalence of pathogenic mutations in five genes (NPHS2, TRPC6, ACTN4, INF2 and PLCE1) and of APOL1 risk alleles (G1 and G2) was ascertained in children and adults diagnosed between 1984 and 2011 with FSGS by renal biopsy.
First, susceptibility to focal segmental glomerulosclerosis (FSGS) and glomerular disease is associated with an APOL1 sequence variant, is expressed in podocytes and encodes apolipoprotein L1, an important component of HDL.
APOL1 risk variants have been shown to be strongly associated with an increased risk for non-diabetic kidney disease including HIV nephropathy, primary non-monogenic focal and segmental glomerulosclerosis, and hypertension-attributed nephropathy among African ancestry populations in the USA.
APOL1 nephropathy comprises a disease spectrum (perhaps with distinct endophenotypes), including focal segmental glomerulosclerosis, collapsing glomerulopathy, and arterionephrosclerosis.
Using this approach, we found novel or known COL4A3 or COL4A5 mutations in a subset of patients with clinically diagnosed or suspected AS, APOL1 variants associated with FSGS in African Americans and novel mutations in genes associated with nephrotic syndrome.
Considerable attention has been focused on how the APOL1/MYH9 locus determines susceptibility to focal segmental glomerulosclerosis, including HIV-associated nephropathy (HIVAN).