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

• Published in: Journal of molecular neuroscience Vol. 71; no. 10; pp. 2142 - 2151
• Main Authors: Liu, Cheng, Guan, Tianwang, Lai, Yanxian, Shen, Yan
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2021; Springer Nature B.V
• Subjects: Aged; Apolipoprotein B; Apolipoproteins; Biomedical and Life Sciences; Biomedicine; Cell Biology; China; Cholesterol; Correlation; Density; Dyslipidemia; Dyslipidemias - blood; Dyslipidemias - epidemiology; Dyslipidemias - genetics; Female; Gene polymorphism; Health risks; Humans; Hypertension; Hypertension - blood; Hypertension - epidemiology; Hypertension - genetics; Ischemia; Ischemic Stroke - blood; Ischemic Stroke - epidemiology; Ischemic Stroke - genetics; KATP Channels - genetics; Male; Metabolic disorders; Metabolism; Middle Aged; Neurochemistry; Neurology; Neurosciences; Patients; Polymorphism, Single Nucleotide; Potassium; Potassium channels; Prevention; Proteomics; Risk; Stroke; Triglycerides; China; Hypertension; Ischemic stroke; ATP-sensitive potassium channels; Dyslipidemia; Polymorphism
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-020-01761-y

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.