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Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes
Type 2 diabetes (T2D) is characterized by increased levels of blood glucose but is increasingly recognized as a heterogeneous disease, especially its multiple discrete cardiovascular phenotypes. Genetic variations play key roles in the heterogeneity of diabetic cardiovascular phenotypes. This study...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984103/ https://www.ncbi.nlm.nih.gov/pubmed/35402560 http://dx.doi.org/10.3389/fcvm.2022.816847 |
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author | Liu, Cheng Lai, Yanxian Guan, Tianwang Zhan, Junfang Pei, Jingxian Wu, Daihong Ying, Songsong Shen, Yan |
author_facet | Liu, Cheng Lai, Yanxian Guan, Tianwang Zhan, Junfang Pei, Jingxian Wu, Daihong Ying, Songsong Shen, Yan |
author_sort | Liu, Cheng |
collection | PubMed |
description | Type 2 diabetes (T2D) is characterized by increased levels of blood glucose but is increasingly recognized as a heterogeneous disease, especially its multiple discrete cardiovascular phenotypes. Genetic variations play key roles in the heterogeneity of diabetic cardiovascular phenotypes. This study investigates possible associations of ATP-sensitive potassium channel (KATP) variants with cardiovascular phenotypes among the Chinese patients with T2D. Six hundred thirty-six patients with T2D and 634 non-diabetic individuals were analyzed in the study. Nine KATP variants were determined by MassARRAY. The KATP rs2285676 (AA + GA, OR = 1.43, 95% CI: 1.13–1.81, P = 0.003), rs1799858 (CC, OR = 1.42, 95% CI: 1.12–1.78, P = 0.004), and rs141294036 (CC, OR = 1.45, 95% CI: 1.15–1.83, P = 0.002) are associated with increased T2D risk. A follow-up of at least 45.8-months (median) indicates further association between the 3 variants and risks of diabetic-related cardiovascular conditions. The associations are categorized as follows: new-onset/recurrent acute coronary syndrome (ACS) (rs2285676/AA + GA, HR = 1.37, 95% CI: 1.10–1.70, P = 0.005; rs141294036/TT + CT, HR = 1.59, 95% CI: 1.28–1.99, P < 0.001), new-onset stroke (rs1799858/CC, HR = 2.58, 95% CI: 1.22–5.43, P = 0.013; rs141294036/CC, HR = 2.30, 95% CI: 1.16–4.55, P = 0.017), new-onset of heart failure (HF) (rs1799858/TT + CT, HR = 2.78, 95% CI: 2.07–3.74, P < 0.001; rs141294036/TT + CT, HR = 1.45, 95% CI: 1.07–1.96, P = 0.015), and new-onset atrial fibrillation (AF) (rs1799858/TT + CT, HR = 2.05, 95% CI: 1.25–3.37, P = 0.004; rs141294036/CC, HR = 2.31, 95% CI: 1.40–3.82, P = 0.001). In particular, the CC genotype of rs1799858 (OR = 2.38, 95% CI: 1.11–5.10, P = 0.025) and rs141294036 (OR = 1.95, 95% CI: 1.04–3.66, P = 0.037) are only associated with the risk of ischemic stroke while its counterpart genotype (TT + CT) is associated with the risks of HF with preserved ejection fraction (HFpEF) (rs1799858, OR = 3.46, 95% CI: 2.31–5.18, P < 0.001) and HF with mildly reduced ejection fraction (HFmrEF) (rs141294036, OR = 2.74, 95% CI: 1.05–7.15, P = 0.039). Furthermore, the 3 variants are associated with increased risks of abnormal serum levels of triglyceride (TIRG) (≥ 1.70 mmol/L), low-density lipoprotein cholesterol (LDL-C) (≥ 1.40 mmol/L), apolipoprotein B (ApoB) (≥ 80 mg/dL), apolipoprotein A-I (ApoA-I) level (< 120 mg/dL), lipoprotein(a) Lp(a) (≥ 300 mg/dL) and high-sensitivity C-reactive protein (HsCRP) (≥ 3.0 mg/L) but exhibited heterogeneity (all P < 0.05). The KATP rs2285676, rs1799858, and rs141294036 are associated with increased risks of T2D and its related cardiovascular phenotypes (ACS, stroke, HF, and AF), but show heterogeneity. The 3 KATP variants may be promising markers for diabetic cardiovascular events favoring “genotype-phenotype” oriented prevention and treatment strategies. |
format | Online Article Text |
id | pubmed-8984103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89841032022-04-07 Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes Liu, Cheng Lai, Yanxian Guan, Tianwang Zhan, Junfang Pei, Jingxian Wu, Daihong Ying, Songsong Shen, Yan Front Cardiovasc Med Cardiovascular Medicine Type 2 diabetes (T2D) is characterized by increased levels of blood glucose but is increasingly recognized as a heterogeneous disease, especially its multiple discrete cardiovascular phenotypes. Genetic variations play key roles in the heterogeneity of diabetic cardiovascular phenotypes. This study investigates possible associations of ATP-sensitive potassium channel (KATP) variants with cardiovascular phenotypes among the Chinese patients with T2D. Six hundred thirty-six patients with T2D and 634 non-diabetic individuals were analyzed in the study. Nine KATP variants were determined by MassARRAY. The KATP rs2285676 (AA + GA, OR = 1.43, 95% CI: 1.13–1.81, P = 0.003), rs1799858 (CC, OR = 1.42, 95% CI: 1.12–1.78, P = 0.004), and rs141294036 (CC, OR = 1.45, 95% CI: 1.15–1.83, P = 0.002) are associated with increased T2D risk. A follow-up of at least 45.8-months (median) indicates further association between the 3 variants and risks of diabetic-related cardiovascular conditions. The associations are categorized as follows: new-onset/recurrent acute coronary syndrome (ACS) (rs2285676/AA + GA, HR = 1.37, 95% CI: 1.10–1.70, P = 0.005; rs141294036/TT + CT, HR = 1.59, 95% CI: 1.28–1.99, P < 0.001), new-onset stroke (rs1799858/CC, HR = 2.58, 95% CI: 1.22–5.43, P = 0.013; rs141294036/CC, HR = 2.30, 95% CI: 1.16–4.55, P = 0.017), new-onset of heart failure (HF) (rs1799858/TT + CT, HR = 2.78, 95% CI: 2.07–3.74, P < 0.001; rs141294036/TT + CT, HR = 1.45, 95% CI: 1.07–1.96, P = 0.015), and new-onset atrial fibrillation (AF) (rs1799858/TT + CT, HR = 2.05, 95% CI: 1.25–3.37, P = 0.004; rs141294036/CC, HR = 2.31, 95% CI: 1.40–3.82, P = 0.001). In particular, the CC genotype of rs1799858 (OR = 2.38, 95% CI: 1.11–5.10, P = 0.025) and rs141294036 (OR = 1.95, 95% CI: 1.04–3.66, P = 0.037) are only associated with the risk of ischemic stroke while its counterpart genotype (TT + CT) is associated with the risks of HF with preserved ejection fraction (HFpEF) (rs1799858, OR = 3.46, 95% CI: 2.31–5.18, P < 0.001) and HF with mildly reduced ejection fraction (HFmrEF) (rs141294036, OR = 2.74, 95% CI: 1.05–7.15, P = 0.039). Furthermore, the 3 variants are associated with increased risks of abnormal serum levels of triglyceride (TIRG) (≥ 1.70 mmol/L), low-density lipoprotein cholesterol (LDL-C) (≥ 1.40 mmol/L), apolipoprotein B (ApoB) (≥ 80 mg/dL), apolipoprotein A-I (ApoA-I) level (< 120 mg/dL), lipoprotein(a) Lp(a) (≥ 300 mg/dL) and high-sensitivity C-reactive protein (HsCRP) (≥ 3.0 mg/L) but exhibited heterogeneity (all P < 0.05). The KATP rs2285676, rs1799858, and rs141294036 are associated with increased risks of T2D and its related cardiovascular phenotypes (ACS, stroke, HF, and AF), but show heterogeneity. The 3 KATP variants may be promising markers for diabetic cardiovascular events favoring “genotype-phenotype” oriented prevention and treatment strategies. Frontiers Media S.A. 2022-03-23 /pmc/articles/PMC8984103/ /pubmed/35402560 http://dx.doi.org/10.3389/fcvm.2022.816847 Text en Copyright © 2022 Liu, Lai, Guan, Zhan, Pei, Wu, Ying and Shen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Liu, Cheng Lai, Yanxian Guan, Tianwang Zhan, Junfang Pei, Jingxian Wu, Daihong Ying, Songsong Shen, Yan Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes |
title | Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes |
title_full | Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes |
title_fullStr | Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes |
title_full_unstemmed | Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes |
title_short | Associations of ATP-Sensitive Potassium Channel’s Gene Polymorphisms With Type 2 Diabetes and Related Cardiovascular Phenotypes |
title_sort | associations of atp-sensitive potassium channel’s gene polymorphisms with type 2 diabetes and related cardiovascular phenotypes |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984103/ https://www.ncbi.nlm.nih.gov/pubmed/35402560 http://dx.doi.org/10.3389/fcvm.2022.816847 |
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