Cardiac Manifestations of KCNK17 Mutations and/or Polymorphisms: A Systematic Review

ABSTRACT Background and Aims The KCNK17 gene encodes k2p17.1 channels (TASK‐4 or TALK‐2) with dominant expressions in the atria and the Purkinje fibers. Emerging studies have suggested possible associations between KCNK17 variants and cardiovascular as well as cerebrovascular diseases. This review aimed to systematically evaluate the evidence on KCNK17 mutations and/or polymorphisms in cardiovascular diseases (primary outcome) and cerebrovascular diseases (secondary outcome). Given the fragmented and limited evidence, a systematic review is warranted to summarize current knowledge and clarify potential clinical implications. Methods PubMed, MEDLINE, Embase, Web of Science, and Scopus were searched for studies evaluating any cardiovascular or cerebrovascular diseases associated with KCNK17 published up to August 1, 2023. Inclusion criteria were original studies reporting KCNK17 mutations and/or polymorphisms in relation to cardiovascular diseases (primary outcome) or cerebrovascular diseases (secondary outcome). Exclusion criteria were studies evaluating pharmacological interventions on the K2P17.1 (TALK‐2) channel, as well as reviews, editorials, and non‐original articles. Results Nine studies concerning KCNK17 were finally included in the systematic review. Six studies evaluated cardiovascular diseases, including atrial fibrillation, cancer‐induced cardiac dysfunction, long QT syndrome, and progressive cardiac conduction defects, and 3 studies evaluated cerebrovascular diseases, including ischemic stroke and cerebral hemorrhage. Conclusions Recent genetic discoveries in the aforementioned diseases warrant further research to develop innovative cardiovascular treatments based on KCNK17.