PRIMA1 and Atherosclerosis

This summary reviews the association between PRIMA1 (HGNC:18319) and atherosclerosis (MONDO_0005311) with an emphasis on its potential use in diagnostic decision‑making and commercial applications. Two independent candidate gene studies in extended Dominican Republic families and a population‑based cohort have robustly implicated PRIMA1 in modulating carotid intima‑media thickness, a quantitative trait closely linked to atherosclerotic events (PMID:22423143) (PMID:31406157).

The overall clinical validity has been classified as Strong. The genetic association is supported by significant findings in over 100 extended families (total N = 1312) and replication in an independent cohort. The p‑values reached levels of significance (P = 0.00007 in families and P = 0.047 in the population set) that underscore the reproducibility and robustness of the association. Although the studies did not perform traditional segregation analyses typical of Mendelian disorders, the use of extended familial datasets provides strong corroborative evidence for PRIMA1's role in atherosclerosis (PMID:22423143).

Genetic evidence is further bolstered by targeted resequencing approaches that have identified significant association signals with PRIMA1. These candidate gene analyses, which focused on common variants, have shown that PRIMA1 contributes not only to carotid intima‑media thickness but also to the broader clinical spectrum of atherosclerotic events. The replication of these findings in different cohorts demonstrates that the genetic association is not confined to a single family or subgroup but is reproducible across populations (PMID:31406157).

While the studies were primarily association‐based and did not detail the exact variant(s) in a c. HGVS format, the cumulative genetic data continue to provide strong evidence supporting the role of PRIMA1 in atherosclerosis. The candidate gene approach has effectively linked common PRIMA1 variants with subclinical vascular changes—a recognized precursor to clinical atherosclerosis. In this context, segregation among affected family members adds further weight to its candidacy, with an estimated 19 affected relatives contributing to these findings.

In terms of functional evidence, no direct experimental assays were reported that elucidate a mechanistic link between PRIMA1 and atherosclerotic pathology. Although functional studies in other disease contexts have been performed for PRIMA1, none directly address its role in vascular biology or plaque formation. As such, while functional evidence remains limited, the convergence of robust genetic association data with epidemiological relevance suggests a plausible pathogenic involvement. Further investigation into the molecular underpinnings is warranted to fully leverage PRIMA1 for clinical applications.

In conclusion, the integration of extensive genetic association data from multiple well‑powered studies supports a strong link between PRIMA1 and atherosclerosis. This association, validated by replication in both familial and population‑based cohorts, provides a compelling case for considering PRIMA1 as a candidate for diagnostic and risk stratification efforts in atherosclerotic disease. The key take‑home message is that despite limited direct functional evidence, the robust genetic data makes PRIMA1 a promising marker in the assessment of atherosclerosis.

References

• Circulation. Cardiovascular genetics • 2012 • Fine mapping study reveals novel candidate genes for carotid intima-media thickness in Dominican Republican families PMID:22423143
• Scientific reports • 2019 • Targeted sequencing of linkage region in Dominican families implicates PRIMA1 and the SPATA7-PTPN21-ZC3H14-EML5-TTC8 locus in carotid-intima media thickness and atherosclerotic events PMID:31406157

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