Pseudohypoxia caused by germline genetic alterations in the VHL gene is associated with increased diabetes and cardiovascular risk: a UK biobank study
Authors' conclusion
VHL gene variant carriers have an increased risk of diabetes and CVA. Mediation analysis suggests pseudohypoxia as a possible mechanism.
Study context
- Population
- UK Biobank participants with genomic and clinical data
- Participants
- 460,430 participants
- Exposure
- VHL gene variant carriers vs non-carriers
- VHL variant carriersn = 2,516
- Outcome
- Metabolic and cardiovascular outcomes (diabetes, cerebrovascular accidents (CVA))
Methodological detailsUK Biobank, exome analysis
- UK Biobank
- Exome analysis
Main finding
As reported in the abstract
- Risk increase more pronounced in higher severity variants
- VHL variant carriers vs Non-carriers: P = 0.04
- VHL variant carriers vs Non-carriers: P = 0.03
Observational data: associations, not effects.
Further findings
Diabetes risk with 5'UTR variants, multivariable analysis
| OR (95% CI) | P value | ||
|---|---|---|---|
| 5'UTR variantsMultivariable analysis | 2.97 (1.78–4.80) | P < 0.001 | |
| 0.20.5125Odds ratio (log scale) |
| Outcome | P value |
|---|---|
| Diabetes risk and age at diabetes diagnosis, 5'UTR variants vs other variants5'UTR variants vs Other variants · increased risk with 5'UTR | P < 0.001 |
| Diabetes risk and age at diabetes diagnosis, 5'UTR variants vs other variants5'UTR variants vs Other variants · younger with 5'UTR | P = 0.003 |
Reticulocytes and metabolic markers
- Increasing reticulocyte levels positively correlated with serum glucose, HbA1c and TG, and mediated the increased diabetes risk of 5'UTR variant carriers
Original publication
Pseudohypoxia caused by germline genetic alterations in the VHL gene is associated with increased diabetes and cardiovascular risk: a UK biobank study. Cardiovasc Diabetol. Published 4 June 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →