A non-coding signature in SHROOM3 is associated with kidney disease progression in Fabry disease

Levstek, Tina (avtor), Breznik, Nika (avtor), Balant Marin, Kaja (avtor), Podkrajšek, Tisa (avtor), Vujkovac, Bojan (avtor), Nowak, Albina (avtor), Oliveira, João-Paulo (avtor), Dostálová, Gabriela (avtor), Linhart, Aleš (avtor), Šafaříková, Marketa (avtor), Altarescu, Gheona (avtor), Trebušak Podkrajšek, Katarina (avtor)

Fabry disease is a rare, X-linked lysosomal storage disorder that often leads to progressive kidney dysfunction. Despite carrying the same pathogenic GLA variant, patients exhibit considerable variability in the onset and progression of Fabry nephropathy, suggesting the involvement of additional genetic modifiers. This study aimed to investigate the possible role of genetic polymorphisms in non-coding regions. A total of 284 patients with Fabry disease were included in the study and divided into two groups based on the progression of the kidney disease. Ten selected single nucleotide polymorphisms located in non-coding regions of podocyterelated genes were analyzed using quantitative PCR with TaqMan probes. The analysis revealed significant associations between specific genotypes and an increased risk of rapid progression of Fabry nephropathy. In particular, the rs9992101 and rs17319721 polymorphisms in the SHROOM3 gene were significantly associated with higher odds of accelerated kidney function decline. However, neither of these polymorphisms nor the polygenic risk scores were associated with conventional biomarkers of kidney disease. Our results suggest that non-coding genetic variants in podocyte-related genes may contribute to the phenotypic variability observed in Fabry nephropathy. The integration of such genetic biomarkers into clinical practice could improve early risk stratification, support more individualized patient monitoring, and facilitate therapeutic decision-making.

• Jezik: Angleški jezik
• Ključne besede: Fabry disease, nephropathy, non-coding variants, podocytes, genetic modifiers, single nucleotide polymorphisms
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 9 str.
• Številčenje: Vol. 147, iss. 1, art. 109710
• PID: 20.500.12556/RUL-182845
• UDK: 61:577.2
• ISSN pri članku: 1096-7206
• DOI: 10.1016/j.ymgme.2025.109710
• COBISS.SI-ID: 263408387
• Datum objave v RUL: 25.05.2026

Gradivo je del revije

• Naslov: Molecular genetics and metabolism
• Skrajšan naslov: Molec. genet. metab.
• Založnik: Elsevier
• ISSN: 1096-7206
• COBISS.SI-ID: 512666137

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: Fabrijeva bolezen, nekodirajoče spremembe, podociti, genetski modifikatorji, polimorfizem posameznega nukleotida

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0170
• Naslov: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: J3-50113
• Naslov: Prepoznavanje in longitudinalna opredelitev bioloških označevalcev razvoja in napredovanja nefropatije pri Fabryjevi bolezni