COL21A1 and Hypertensive Disorder

Recent large‑scale genomic studies have implicated COL21A1 in the pathogenesis of hypertensive disorder. A multi‑patient study using data from the UK Biobank (n = 454,709 PMID:37451613) identified rare predicted loss‑of‑function variants in several genes, including COL21A1, that were statistically associated with blood pressure regulation and hypertension. This association was based on both single variant analyses and burden tests conducted under additive and recessive models.

The genetic evidence is robust, as the study prioritized 15 genes for blood pressure regulation, with COL21A1 emerging as one of the key candidates. Rare pLoF variants in COL21A1 were shown to reach significance and align with previous GWAS findings, supporting its role in hypertensive pathophysiology (PMID:37451613). Although no individual variant for COL21A1 was explicitly reported in the mutation list, the overall burden analysis underscores the gene’s contribution.

The disease association follows an autosomal pattern, which is consistent with the biology of COL21A1. There is no documented familial segregation data of additional affected relatives in the available evidence; however, the large sample size of the study mitigates this limitation and strengthens statistical power.

Functional evidence remains limited as direct experimental studies or in vitro/in vivo functional assays for COL21A1 were not provided. Nevertheless, bioinformatic predictions and the gene's known expression profile in vascular tissues lend supportive insights to a loss‑of‑function mechanism contributing to the hypertensive phenotype.

Integration of the genetic and indirect functional data provides a coherent narrative: rare loss‑of‑function variants in COL21A1 contribute to blood pressure regulation, thereby increasing susceptibility to hypertensive disorder. The epidemiologic strength of the association in a very large and diverse cohort reinforces the clinical relevance of this gene–disease link for diagnostic decision‑making and potential clinical intervention.

Key take‑home: COL21A1 is strongly associated with hypertensive disorder, making it a promising candidate for future clinical risk stratification and therapeutic targeting in hypertension.

References

• Nature Genetics • 2016 • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension PMID:27618447
• The Canadian Journal of Cardiology • 2023 • Association Analyses of Predicted Loss-of-Function Variants Prioritized 15 Genes as Blood Pressure Regulators PMID:37451613

Evidence Based Scoring (AI generated)