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Clinical and Genetic Analysis of KATP Variants With Heart Failure Risk in Patients With Decreased Serum ApoA-I Levels

Cheng Liu1, Yanxian Lai1, Jingxian Pei2

  • 1Department of Cardiology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, China.

The Journal of Clinical Endocrinology and Metabolism
|May 13, 2021
PubMed

Insights

Genetic variants in adenosine triphosphate-sensitive potassium channels (KATP) are linked to lower apolipoprotein A-I (ApoA-I) levels and increased heart failure (HF) risk. Specifically, KATP rs141294036 predicts higher risks of HF incidence and rehospitalization.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Biomarker Discovery

Background:

  • Low serum apolipoprotein A-I (ApoA-I) concentration is a known risk factor for heart failure (HF).
  • Adenosine triphosphate-sensitive potassium channels (KATP) are emerging targets for HF management due to their role in vascular and metabolic regulation.
  • The KATP gene exhibits significant genetic heterogeneity and polymorphism.

Purpose of the Study:

  • To investigate the association between KATP gene variants and the risk of decreased ApoA-I levels.
  • To determine if KATP variants predict the incidence and rehospitalization risk of heart failure (HF), particularly HF with preserved ejection fraction (HFpEF).
  • To explore the role of exosome-derived microRNAs (exo-miRs) in mediating the relationship between KATP variants and HF risk.

Main Methods:

  • Retrospective analysis of 634 individuals (317 with low ApoA-I, 317 controls).
  • Genotyping of five KATP variants using MassARRAY and next-generation sequencing for exo-miR profiling.
  • Validation of top differentially expressed exo-miRs in a separate cohort of 240 individuals with low ApoA-I.

Main Results:

  • The KATP rs141294036 variant was significantly associated with lower ApoA-I levels (OR=1.95) and increased HF incidence (OR=2.38), especially HFpEF (OR=2.13).
  • Carriers of the rs141294036 CC genotype showed a higher risk of HF rehospitalization (HR=1.91) during a median 48.6-month follow-up.
  • Five specific exo-miRs (miR-31-5p, miR-126-5p, miR-106a-5p, miR-378i, miR-181c-5p) were confirmed to be differentially expressed between KATP genotypes in individuals with low ApoA-I.

Conclusions:

  • KATP rs141294036 is a significant genetic predictor of reduced ApoA-I levels, HF incidence, and HF rehospitalization.
  • The identified exo-miRs and their associated metabolic pathways may play a role in the KATP-mediated risk of HF.
  • These findings highlight KATP variants as potential therapeutic targets and biomarkers for HF risk stratification.
Abstract

Keywords:
ATP-sensitive potassium channelsapolipoprotein A-Iexosome-derived microRNAsgenetic polymorphismheart failure

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