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Association of KATP Gene Polymorphisms with Dyslipidemia and Ischemic Stroke Risks Among Hypertensive Patients in South China

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Abstract

ATP-sensitive potassium channels (KATP) couple vascular reactivity and metabolism with ischemic protection which makes them potential targets for prevention and management of ischemic stroke (IS). This study investigates the potential association between KATP polymorphisms and hypertension (HTN), dyslipidemia, and consequently ischemic stroke (IS). Nine hundred and fourteen (914) patients genotyped for KATP polymorphisms (rs2285676, rs1799858, rs4148671, rs61928479, and rs141294036) were analyzed. KATP rs141294036 (CC, adjusted OR = 1.59, 95%CI: 1.17–2.14, P = 0.003) was related to higher HTN risk. Meanwhile, rs2285676 (AA + GA, adjusted OR = 1.53, 95%CI: 1.08–2.19, P = 0.018) was associated with increased triglyceride level (≥ 1.7 mmol/L). rs2285676 (AA + GA, adjusted OR = 1.80, 95% CI: 1.24–2.61, P = 0.002), rs1799858 (TT + CT, adjusted OR = 1.68, 95% CI: 1.17–2.42, P = 0.005), and rs141294036 (TT + CT, adjusted OR = 1.90, 95% CI: 1.30–2.78, P = 0.001) were related to increased low-density lipoprotein cholesterol (≥ 1.8 mmol/L). rs2285676 (AA + GA, adjusted OR = 2.57, 95% CI: 1.74–3.82, P < 0.001) and rs141294036 (TT + CT, adjusted OR = 1.93, 95% CI: 1.27–2.93, P = 0.002) were related to increased apolipoprotein B (≥ 65 mg/dL). In addition, the 5 KATP polymorphisms were non-correlated with three types of dyslipidemia (total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein AI). After median 50.6 month of follow-up, participants carrying CC genotype of rs141294036 showed correlation with elevated risk of new onset IS (adjusted HR = 2.55, 95% CI: 1.23–5.27, P = 0.012). These novel findings suggest that KATP rs141294036 is associated with increased risk of HTN, dyslipidemia, and IS. Based on these correlations, KATP rs141294036 could be a promising target for early and personalized therapeutics as well as prevention strategies for the aforementioned clinical pathologies.

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Data Availability

The datasets used and/or analyzed in this study are available from the corresponding author on reasonable request.

Abbreviations

ACE:

Angiotensin converting enzyme

ACR:

Urinary albumin-to-creative-ratio

Alb:

Albumin

ALD:

Aldosterone

ALT:

Alanine aminotransferase

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:

Body urea nitrogen

Cr:

Creatinine

DBP:

Diastolic blood pressure

HTN:

Hypertension

FBG:

Fasting blood glucose

HbA1C:

Glycosylated hemoglobin

HDL-C:

High density lipoprotein cholesterol

HsCRP:

High sensitivity C-reactive protein

IR:

Insulin resistance

IS:

Ischemic stroke

KATP:

ATP-sensitive potassium channels

LAD:

Left atrial end-diastolic dimension

LDL-C:

Low-density lipoprotein cholesterol

Lp(a):

Lipoprotein A

LVD:

Left ventricular end-diastolic diameter

LVEF:

Left ventricular ejection fraction

MAF:

Minor allele frequency

P2hBS:

2-Hour postprandial blood sugar

RAAS:

Renin-angiotensin-aldosterone system

RAD:

Right atrial end diastolic dimension

RVD:

Right ventricular end-diastolic diameter

SBP:

Systolic blood pressure

SNPs:

Single nucleotide polymorphisms

TC:

Total cholesterol

T2D:

Type 2 diabetes mellitus

TRIG:

Triglyceride

UA:

Blood uric acid

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Acknowledgments

The authors wish to thank all the study participants from the South China Cardiovascular Related Disease Cohort (SCCDC, since July 2010), research staff, and students who participated in this work.

Funding

This study was funded by the National Natural Science Foundation of China (81100235), the Guangdong Natural Science Foundation of China (S2011040004458), the Guangdong Science and Technology Planning Project of China (2014A020212372), the Guangzhou Science and Technology Project of China (2012J4100035 and 201804010214), and Xinxin-Merck Cardiovascular Scientific Research Fund (2017-CCA-xinxin merck fund-012).

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Authors and Affiliations

  1. Department of Cardiology, Guangzhou First People’s Hospital, South China University of Technology, #1 Panfu road, Guangzhou, 510180, China

    Cheng Liu & Yanxian Lai

  2. Department of Cardiology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, 510180, China

    Cheng Liu, Tianwang Guan & Yan Shen

Authors
  1. Cheng Liu
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  2. Tianwang Guan
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  3. Yanxian Lai
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  4. Yan Shen
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Contributions

CL, literature search, study format, protocol writing, data collection, data processing, data interpretation, data analysis, manuscript writing; YXL, literature search, patients’ recruitment, data interpretation, and manuscript writing; TWG, carrying out the molecular genetics; TWG and YS, patients’ recruitment, data collection, patients’ follow-up. The manuscript has been read and approved by all authors.

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Correspondence to Cheng Liu.

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The authors declare that they have no conflict of interest.

Ethics Approval

The study received ethics approval from the Institutional Review Board of Guangzhou First People’s Hospital (K-2017-043-02). All procedures performed in studies involving human participants were in accordance with the ethics guidelines of the institutional and with the principles of the Declaration of Helsinki.

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Liu, C., Guan, T., Lai, Y. et al. Association of KATP Gene Polymorphisms with Dyslipidemia and Ischemic Stroke Risks Among Hypertensive Patients in South China. J Mol Neurosci 71, 2142–2151 (2021). https://doi.org/10.1007/s12031-020-01761-y

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