CABCOCO1 and Hypertensive Disorder

This summary evaluates the association between CABCOCO1 (HGNC:28678) and hypertensive disorder (MONDO_0005044) based on multi‐patient genetic studies. Two independent genome‑wide association studies reported significant associations with blood pressure traits, linking common variants near CABCOCO1 to the hypertensive phenotype (PMID:19430483, PMID:22071413).

The primary study, published in Nature Genetics (2009), evaluated 34,433 subjects with extensive follow‑up in cohorts exceeding 70,000 subjects. The extremely significant p‑values (e.g., P = 7 × 10⁻²⁴ for CYP17A1 and similar robust associations for loci including CABCOCO1) support a strong genetic association with blood pressure and, by extension, hypertensive disorder (PMID:19430483).

A replication study in a Japanese cohort (N = 1279) further demonstrated that risk alleles at the CABCOCO1 locus were associated with continuous blood pressure measurements and dichotomous hypertension. This multi‑ethnic replication reinforces the validity of the association and indicates that the signal is not population‑specific (PMID:22071413).

Genetic evidence is drawn from robust GWAS data where additive models revealed that common variants, including those near CABCOCO1, contribute to blood pressure regulation. Although the specific causal variant for CABCOCO1 was not detailed in the reports, the overall association signal remains statistically compelling.

No explicit familial segregation data were provided for CABCOCO1, as the association derives from population‑based studies rather than traditional pedigree analyses. Consequently, while case‐control genetic data are strong, detailed variant-level mechanistic insights are currently lacking.

Functional evidence remains limited for CABCOCO1, with no direct experimental studies reported to clarify the biological mechanism linking the gene to hypertensive disorder. Further functional assessments, such as cellular assays and animal models, are needed to elucidate the underlying pathogenicity, which currently restricts the functional evidence score.

In conclusion, the consistent genetic association from large cohorts and replication studies provides a compelling case for CABCOCO1’s involvement in hypertensive disorder. While additional experimental data are warranted, this evidence is already of considerable clinical utility, supporting diagnostic decision‑making and informing potential precision strategies.

References

• Nature Genetics • 2009 • Genome‑wide association study identifies eight loci associated with blood pressure PMID:19430483
• Journal of Human Genetics • 2012 • Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women PMID:22071413

Evidence Based Scoring (AI generated)