Objective: Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor of genes affecting the vascular endothelium as well as lipid metabolism. A phenotype associated with genetic variation in ZNF202 is presently unknown. We tested the hypothesis that a common variant in ZNF202, A154V, predicts risk of ischemic heart disease (IHD), myocardial infarction (MI), and ischemic cerebrovascular disease (ICVD).
Methods and results: We conducted a prospective study of more than 9000 individuals from the general population with 24 years follow-up. In women, age-adjusted hazard ratios in heterozygotes and homozygotes versus non-carriers were 1.2 (95% CI: 1.0-1.5, P = 0.04) and 1.5 (1.1-2.1, P = 0.007) for IHD, 1.5 (1.1-2.1; P = 0.01) and 1.7 (1.1-2.8, P = 0.02) for MI, and 1.3 (1.0-1.8, P = 0.07) and 1.3 (0.8-2.1; P = 0.33) for ICVD. Adjustments for lipids and lipoproteins did not alter these hazard ratios substantially. Genotype did not predict risk in men. Finally, results for IHD were borderline significant (P = 0.06) in an independent case-control study including 933 patients and 8068 controls.
Conclusion: This is the first study to suggest that ZNF202 could be a new candidate gene for IHD and MI in the general population.