Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.
Pediatr Nephrol
; 38(6): 1793-1800, 2023 06.
Article
de En
| MEDLINE
| ID: mdl-36357634
ABSTRACT
BACKGROUND:
Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.METHODS:
We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.RESULTS:
The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.CONCLUSIONS:
The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Glomérulonéphrite segmentaire et focale
/
Glomérulonéphrite extra-membraneuse
/
Néphrose lipoïdique
/
Syndrome néphrotique
Type d'étude:
Etiology_studies
/
Risk_factors_studies
Limites:
Child
/
Humans
Langue:
En
Journal:
Pediatr Nephrol
Sujet du journal:
NEFROLOGIA
/
PEDIATRIA
Année:
2023
Type de document:
Article
Pays d'affiliation:
Royaume-Uni