Research Paper Volume 13, Issue 6 pp 8177—8203
Genetic predisposition and bioinformatics analysis of ATP-sensitive potassium channels polymorphisms with the risks of elevated apolipoprotein B serum levels and its related arteriosclerosis cardiovascular disease
- 1 Department of Cardiology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou 510180, China
- 2 Department of Health Management Center, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou 510180, China
Received: June 19, 2020 Accepted: January 21, 2021 Published: March 3, 2021
https://doi.org/10.18632/aging.202628How to Cite
Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Serum concentration of apolipoprotein B (Apo B) is causally associated with arteriosclerosis cardiovascular disease (ASCVD) risk. Whether ATP-sensitive potassium channels (KATP) variants predict the risk of increased Apo B concentration (≥ 80 mg/dL) and related ASCVD remain less clear. We recruited 522 subjects with elevated Apo B concentration (≥ 80 mg/dL) and 522 counterpart subjects (< 80 mg/dL) from South China to assess the associations of KATP variants (rs11046182, rs78148713, rs145456027 and rs147265929) with the risks of increased Apo B serum concentration (≥ 80 mg/dL), carotid artery stenosis (CAS) ≥ 50% and new-onset ischemic stroke (IS). Our results showed that only KATP SNP rs11046182 (GG genotype) was associated with increased risk of Apo B ≥ 80 mg/dL (adjusted OR=2.17, P<0.001) and CAS ≥ 50% (adjusted OR=2.63, P=0.011). After median 50.6-months follow-up, subjects carrying GG genotype of rs11046182 were associated with higher risk of new-onset IS (adjusted HR=2.24, P=0.024). Further, the exosome-derived microRNAs (exo-miRs) expression profile was identified by next-generation sequencing. 41 exo-miRs were significantly differentially expressed under cross-talk status between high Apo B level (≥ 80 mg/dL) and KATP rs11046182. Our study demonstrated that KATP variant rs11046182 was associated with higher risks of elevated serum Apo B levels and its related ASCVD, and the possible mechanism was related to specific exo-miRs expression profile of KATP rs11046182.
Abbreviations
ABCA1: ATP binding cassette subfamily A member 1; ACE: angiotensin converting enzyme; AF: atrial fibrillation; Alb: albumin; ALD: aldosterone; ALT: alanine aminotransferase; AMI: acute myocardial infarction; Ang I/ II: angiotensin I/II; Apo AI: apolipoprotein AI; Apo B: apolipoprotein B; ASCVD: arteriosclerosis cardiovascular disease; AST: aspartate aminotransferase; BMI: body mass index; BUN: blood urea nitrogen; CAS: carotid artery stenosis; CAD: coronary atherosclerotic heart disease; CCBs: calcium channel blockers; CI: confidence interval; CTGs: candidate target genes; CPT1A: carnitine palmitoyltransferase 1A; CYBB: cytochrome b(558) subunit beta; DBP: diastolic blood pressure; DE: differentially expressed; EH: essential hypertension; exo-miRs: exosome-derived microRNAs; FBG: fasting blood glucose; FDR: false discovery rate; GO: Gene Ontology; HbA1C: glycosylated hemoglobin; HDL-C: high-density lipoprotein cholesterol; HGB: hemoglobin concentration; HIF-1α: hypoxia-inducible factor-1α; HR: hazard ratio; HsCRP: hypersensitive C-reactive protein; IR: insulin resistance; IS: ischemic stroke; JAG1: jagged 1; K+: serum potassium; KATP: ATP-sensitive potassium channels; KEGG: Kyoto Encyclopedia of Genes and Genomes; LDL-C: low-density lipoprotein cholesterol; miR(s): microRNA(s); MAF: minor allele frequency; MAU: microalbuminuria; MRAs: mineralocorticoid receptor antagonists; Na+: serum sodium; Notch1: Notch homolog 1 (translocation-associated); OR: odds ratio; P2hBS: postprandial blood glucose two hours; PLT: platelet count; RAAS: renin-angiotensin-aldosterone system; PFKFB2: 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2; PGC-1α: peroxisome proliferator-activated receptor-gamma coactivator-1α; PPARα: peroxisome proliferator-activated receptor-α; RPM: reads per million; SBP: systolic blood pressure; Scr: serum creatinine; SLC2A1: solute carrier family 2 member 1; SNP: single nucleotide polymorphism; TC: total cholesterol; T2D: type 2 diabetes mellitus; TRIG: triglyceride; UA: serum uric acid; WBC: white blood cell count.