ATP-sensitive potassium channels gene polymorphism rs1799858 affects the risk of macro-/micro-vascular arteriosclerotic event in patients with increased low-density lipoprotein cholesterol levels

Abstract

Background: Plasma concentration of low-density lipoprotein cholesterol (LDL-C) is causally related to the risk of arteriosclerotic events. Whether ATP-sensitive potassium channels (KATP) genetic variants predict increased LDL-C concentration (≥1.8 mmol/L) and risk of macro-/micro-vascular arteriosclerotic event remain elusive.

Methods: A total of 320 subjects with increased LDL-C concentration (≥1.8 mmol/L) and 320 counterpart subjects (< 1.8 mmol/L) from the South China were enrolled in this study. Three KATP polymorphisms (rs1799858, rs4148671 and rs78148713) were genotyped by the Sequenom MassARRAY system. Binary logistic regression analysis was used to evaluate the association of the 3 KATP variants with increased LDL-C concentration and carotid artery stenosis (CAS) ≥50%. Two-way ANOVA was used to analyze the association of the 3 KATP variants with microalbumin in urine (MAU) and high-sensitivity C-reactive protein (HsCRP) levels. Cox proportional hazards regression analysis was used to retrospectively analyse the association of the optimal variant with the risk of new onset/recurrent acute myocardial infarction (AMI).

Results: Among the 3 studied KATP gene single nucleotide polymorphisms (SNPs), only rs1799858 (TT + CT genotype) was associated with elevated risk of LDL-C ≥ 1.8 mmol/L (adjusted OR = 2.25, 95% CI: 1.31-3.85, P = 0.003) and CAS ≥50% (adjusted OR = 2.80, 95% CI: 1.12-6.98, P = 0.028). KATP SNP rs1799858 was also associated with increased MAU (P = 0.013) and HsCRP (P = 0.027) levels. The follow-up for an average of 51.1-months revealed that participants carrying the T-allele (TT + CT) of rs1799858 was associated with high risk of new onset/recurrent AMI (adjusted HR = 2.90, 95% CI: 1.06-7.94, P = 0.038).

Conclusion: The KATP SNP rs1799858 may be an optimal genetic predisposition marker for increased LDL-C concentration (≥1.8 mmol/L) and its related macro-/micro-vascular arteriosclerotic event risk. The KATP variant rs1799858 was associated with higher risk of macro-/micro-vascular arteriosclerotic events in patients with elevated serum LDL-C levels.

Keywords: ATP-sensitive potassium channels; Low-density lipoprotein cholesterol; Microalbumin in urine; Myocardial infarction; Polymorphism.

Fig. 1

Association between KATP rs1799858 and new-onset/recurrent AMI in participants*. *Model 4: After adjustment for gender, age, smoking, drinking, WBC, BMI, liver function (ALT, AST and Alb), renal function (Scr, BUN and UA), HsCRP, HbA1C, HCY, and RAAS activity (ACE, renin, Ang I, Ang II and ALD), dyslipidemia (TRIG, TC, LDL-C, Apo B, HDL-C and Apo AI), medical condition (EH, CAD, T2D and AF), NYHA functional classification, combined medication (antiplatelet drugs, warfarin, statins, RSIs, BBs, MRA, CCBs, diuretics, digoxin, nitrates, and hypoglycemic agents) and echocardiography index (RVD, RAD, LVD, LAD, and LVEF)