Lower serum concentration of apolipoprotein A-I (ApoA-I) is causally associated with heart failure (HF) risk. ATP-sensitive potassium channels (KATP), as a gating channel coupling vascular reactivity and metabolism with ischemic protection, become a new potential target of management for HF. The KATP gene sequence is highly polymorphic and high degree of genetic heterogeneity.To determine whether ATP-sensitive potassium channels (KATP) variants predict the risks of decreased ApoA-I concentration and its related HF.A total of 634 subjects, including 317 subjects with decreased ApoA-I concentration (< 120 mg/dL) and 317 counterpart subjects (≥ 120 mg/dL), were retrospectively selected.5 KATP variants were genotyped through MassARRAY platform. The exosome-derived microRNAs (exo-miRs) expression profiles were identified by next-generation sequencing, and the top 10 DE exo-miRs were verified using qPCR in a validation cohort of 240 subjects with decreased ApoA-I concentration.KATP rs141294036 was related to increased risk of lower ApoA-I levels (adjusted OR=1.95, P=0.002) and HF incidence (adjusted OR=2.38, P=0.009), especially HFpEF (adjusted OR=2.13, P=0.015). After median 48.6-months follow-up, participants carrying CC genotype of rs141294036 was associated with elevated HF re-hospitalization risk (adjusted HR=1.91, P=0.005). 36 exo-miRs were significantly differentially expressed between different genotypes of rs141294036 in subjects with lower ApoA-I levels, but only 5 exo-miRs (miR-31-5p, miR-126-5p, miR-106a-5p, miR-378i and miR-181c-5p) were further confirmed.The KATP rs141294036 was associated with increased risks of lower ApoA-I levels, HF incidence (especially HFpEF) and HF re-hospitalization, involving in those 5 confirmed exo-miRs and its related metabolic pathways.
Cheng Liu, Yanxian Lai, Jingxian Pei, Huiling Huang, Junfang Zhan, Songsong Ying, Yan Shen