Cumulative evidence for associations between variants in the histone deacetylases genes and cardio-cerebrovascular diseases: A systematic review and meta-analysis

<b>Background:</b> A variety of studies have reported the associations between <i>histone deacetylases</i> (<i>HDACs</i>) genes and cardio-cerebrovascular diseases. The identification of variants in the <i>HDACs</i> genes and the determination of risk alleles could open novel therapeutic avenues for these diseases. This article summarized variants in <i>HDACs</i> genes and different sub-types of cardio-cerebrovascular diseases. <b>Methods:</b> A comprehensive literature search was conducted across PubMed, Web of Science and Scopus databases to identify studies published prior to 27 June 2025. We registered this protocol in the PROSPERO database (CRD420251010100). The Venice Criteria were applied to assess the statistically significant associations identified by meta-analyses. The single-nucleotide polymorphisms were mapped to their corresponding genes, and functional annotation was conducted using the Encyclopedia of DNA Elements tool, HaploReg and the UCSC Genome browser. <b>Results:</b> We finally included 34 published studies and 160 datasets to assess the associations between variants in <i>HDAC</i> genes and cardio-cerebrovascular diseases. Rs2107595 in <i>HDAC</i> 9 was the variant found to be associated with four sub-types identified by genome-wide association study or meta-analyses. Rs11984041 was related to ischemic stroke. Rs10230207 and rs2192476 were associated with intracranial aneurysm. <b>Conclusions:</b> <i>HDACs</i> genes were associated with multiple cardio-cerebrovascular diseases. However, ethnic disparities were observed in their effects. Therefore, ethnicity-targeted treatments, including specific HDAC inhibitors, should be developed in the future.