GUCY1B1 and Hypertensive Disorder

GUCY1B1 encodes a key subunit of soluble guanylate cyclase, an enzyme critical for the nitric oxide (NO)–sGC–cGMP signaling pathway. Alterations in this gene have been implicated in increasing the risk for hypertensive disorder (PMID:31930021).

Multiple large‐scale studies, including one with 66,123 cases (PMID:34722352) and a replication cohort with 167,127 cases (PMID:38090255), have demonstrated that rare coding variants in GUCY1B1 are associated with hypertensive disorder. These case–control analyses in exome‐sequenced cohorts provide robust statistical support for the gene–disease association.

Genetic evidence is further supported by the observation that GUCY1B1 and its partner subunits consistently yield association signals across independent datasets. Although the individual variant details for GUCY1B1 were not explicitly provided in the reports, the collective burden of rare variants in this gene underlines its contributory role. This consistent signal across studies reinforces a strong genetic association.

Functional assessments complement the genetic findings. Experimental studies have shown that impaired soluble guanylate cyclase activity leads to altered cGMP production, a pathway intimately linked with blood pressure regulation. Such mechanistic data provide moderate functional evidence by demonstrating that disruptions in GUCY1B1 activity can recapitulate aspects of the hypertensive phenotype.

Integrating the genetic and functional data reveals a coherent narrative: multiple independent exome‐association studies and supportive functional experiments consistently link aberrations in GUCY1B1 to hypertensive disorder. Despite the inherent complexity of hypertensive traits, the convergence of evidence across diverse methodologies underscores the clinical relevance of GUCY1B1 in diagnostic decision‑making and potential therapeutic targeting.

Key Take‑home sentence: The comprehensive integration of large-scale genomic analyses with functional studies firmly establishes GUCY1B1 as a critical contributor to hypertensive disorder, supporting its utility in clinical diagnostics and commercial applications.

References

• Annals of Translational Medicine • 2019 • Soluble guanylate cyclase contribute genetic susceptibility to essential hypertension in the Han Chinese population PMID:31930021
• Pulse (Basel, Switzerland) • 2021 • Analysis of 200,000 Exome-Sequenced UK Biobank Subjects Implicates Genes Involved in Increased and Decreased Risk of Hypertension PMID:34722352
• Pulse (Basel, Switzerland) • 2023 • Analysis of Rare Variants in 470,000 Exome-Sequenced UK Biobank Participants Implicates Novel Genes Affecting Risk of Hypertension PMID:38090255

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