ZNF202 and Myocardial Ischemia

The gene ZNF202 (HGNC:12994) has emerged as a candidate risk gene for myocardial ischemia (MONDO:0024644) based on data from large population‐based studies. Two independent investigations, including one prospective cohort of more than 9000 individuals (PMID:16289551) and replicated case‑control studies with up to 1,549 cases (PMID:18652945), report significant associations between common variants in ZNF202 and ischemic heart disease phenotypes.

The clinical validity of this association is considered Strong according to ClinGen criteria. Although familial segregation data is not available, the compelling evidence arises from multiple independent studies. In one study, hazard ratios for myocardial infarction and ischemic endpoints in women were significantly elevated, with effect sizes derived from robust population follow‑up (PMID:16289551).

Genetic evidence further supports this link, with case reports and large series documenting the variant spectrum including the missense variant c.461C>T (p.Ala154Val). This variant exemplifies the type of coding change reported in association with myocardial ischemia and underscores the role of ZNF202 in modulating risk. The studies also highlight that additional common single nucleotide polymorphisms in the gene contribute to the overall risk profile.

Functional evidence complements genetic findings. In vitro experiments demonstrated that a promoter variant (g.-660A>G) in ZNF202 reduces transcriptional activity by 60% (PMID:18652945), suggesting a mechanism involving impaired transcriptional repression of genes important for vascular homeostasis and lipid metabolism. The experimental data support a model of pathogenicity in which reduced ZNF202 activity leads to vascular dysregulation and increased susceptibility to myocardial ischemia.

Overall, the integration of genetic and functional data provides a coherent narrative supporting a strong association between ZNF202 and myocardial ischemia. The convergent evidence from large-scale association studies and mechanistic in vitro analyses confirms the biological relevance of ZNF202 variants in the disease process. Although additional genes and environmental factors contribute to myocardial ischemia, the data for ZNF202 exceeds standard scoring thresholds and has clear clinical utility for diagnostic decision-making.

Key take‑home: Robust, convergent evidence from epidemiological and functional studies substantiates the role of ZNF202 in myocardial ischemia, underscoring its value for clinical assessments and future research endeavors.

References

• Atherosclerosis • 2006 • Zinc Finger Protein 202: a new candidate gene for ischemic heart disease: The Copenhagen City Heart Study PMID:16289551
• Journal of the American College of Cardiology • 2008 • Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease PMID:18652945

Evidence Based Scoring (AI generated)