Association of KATP Variants With CMD and RAP in CAD Patients With Increased Serum Lipoprotein(a) Levels
Author:
Pei Jingxian1, Liu Cheng23ORCID, Yang Zhengxia4, Lai Yanxian2, Zhang Shenghui25, Guan Tianwang2, Shen Yan2
Affiliation:
1. Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University , Guangzhou 510260 , China 2. Department of Cardiology, Guangzhou First People's Hospital, South China University of Technology , Guangzhou 510180 , China 3. Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University , Guangzhou 510180 , China 4. Department of Electronic Business, School of Economics and Finance, South China University of Technology , Guangzhou 510006 , China 5. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180 , China
Abstract
Abstract
Context
Refractory angina pectoris (RAP) is a specific subtype of coronary artery disease (CAD). Lipoprotein(a) [Lp(a)] and its induced coronary microvascular dysfunction (CMD) play an important role in pathogenesis of RAP, but its metabolism was mostly genetically determined. The adenosine triphosphate (ATP)-sensitive potassium channel (KATP) is involved in lipid metabolism and microvascular homeostasis and becomes a promising target for the management of Lp(a) and its related RAP.
Objective
To investigate associations of KATP variants with hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD.
Design, Patients, Settings
A total of 1148 newly diagnosed patients with CAD were prospectively selected and divided into control (Lp(a) < 180 mg/dL) and case (Lp(a) ≥ 180 mg/dL, hyperlipoprotein(a)emia) group.
Methods
9 KATP variants were genotyped by MassARRAY system. The expression profile of exosome-derived microRNAs (exo-miRs) was identified by next-generation sequencing, and the expression levels of differentially expressed exo-miRs were evaluated by quantitative RT-PCR in verification cohort.
Results
Three KATP variants were associated with increased risk of hyperlipoprotein(a)emia in patients with CAD as follows: rs2285676 (AA + GA genotype, adjusted odds ratio [OR] = 1.44; 95% CI, 1.10-1.88; P = 0.008), rs1799858 (CC genotype, adjusted OR = 1.33; 95% CI, 1.03-1.73; P = 0.030), and rs141294036 (CC genotype, adjusted OR = 1.43; 95% CI, 1.10-1.87; P = 0.008). Only rs141294036 was associated with increased risk of CMD (CC genotype, adjusted OR = 1.62; 95% CI, 1.23-2.13; P = 0.001), and further with increased RAP risk (CC genotype, adjusted hazard ratio = 2.05; 95% CI, 1.22-3.43; P = 0.007) after median follow-up of 50.6 months. Between the 2 genotypes of rs141294036, 152 exo-miRs were significantly differentially expressed, but only 10 exo-miRs (miR-7110-3p, miR-548az-5p, miR-214-3p, let-7i-5p, miR-218-5p, miR-128-3p, miR-378i, miR-625-3p, miR-128-1-5p, and miR-3187-3p) were further confirmed in patients with RAP with hyperlipoprotein(a)emia and CMD.
Conclusion
KATP rs141294036 may serve a potential genetic marker for hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD.
Funder
Guangzhou Municipal Science and Technology Project of China National Natural Science Foundation of China Natural Science Foundation of Guangdong Province, China Science and Technology Planning Project of Guangdong Province, China
Publisher
The Endocrine Society
Subject
Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism
Reference53 articles.
1. Reappraisal of ischemic heart disease;Kaski;Circulation,2018 2. High prevalence of raised lipoprotein(a) in patients with refractory angina;Khan;Glob Cardiol Sci Pract,2015 3. Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial;Khan;Eur Heart J,2017 4. Treating coronary microvascular dysfunction as the “culprit” lesion in patients with refractory angina: lessons from CorMicA at 1 year;Taqueti;JACC Cardiovasc Interv,2020 5. Lipoprotein(a) predicts a new onset of chronic kidney disease in people with type 2 diabetes mellitus;Yun;Diabet Med,2016
|
|