High prevalence of short telomeres in idiopathic porto-sinusoidal vascular disorder.
Hepatol Commun
; 8(8)2024 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-39037376
ABSTRACT
BACKGROUND:
Telomeres prevent damage to coding DNA as end-nucleotides are lost during mitosis. Mutations in telomere maintenance genes cause excessive telomere shortening, a condition known as short telomere syndrome (STS). One hepatic manifestation documented in STS is porto-sinusoidal vascular disorder (PSVD).METHODS:
As the etiology of many cases of PSVD remains unknown, this study explored the extent to which short telomeres are present in patients with idiopathic PSVD.RESULTS:
This monocentric cross-sectional study included patients with histologically defined idiopathic PSVD. Telomere length in 6 peripheral blood leukocyte subpopulations was assessed using fluorescent in situ hybridization and flow cytometry. Variants of telomere-related genes were identified using high-throughput exome sequencing. In total, 22 patients were included, of whom 16 (73%) had short (9/22) or very short (7/22) telomeres according to age-adjusted reference ranges. Fourteen patients (64%) had clinically significant portal hypertension. Shorter telomeres were more frequent in males (p = 0.005) and patients with concomitant interstitial lung disease (p < 0.001), chronic kidney disease (p < 0.001), and erythrocyte macrocytosis (p = 0.007). Portal hypertension (p = 0.021), low serum albumin level (p < 0.001), low platelet count (p = 0.007), and hyperbilirubinemia (p = 0.053) were also associated with shorter telomeres. Variants in known STS-related genes were identified in 4 patients with VSTel and 1 with STel.CONCLUSIONS:
Short and very short telomeres were highly prevalent in patients with idiopathic PSVD, with 31% presenting with variants in telomere-related genes. Telomere biology may play an important role in vascular liver disease development. Clinicians should consider measuring telomeres in any patient presenting with PSVD.
Full text:
1
Database:
MEDLINE
Main subject:
Telomere Shortening
Limits:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Hepatol Commun
Year:
2024
Type:
Article
Affiliation country:
Switzerland