Key result
Co-presence of KCNJ11 and NOS3 variants linked to ~81% lower ischemic heart disease risk.
Why the study?
Genetic susceptibility may influence ischemic heart disease predisposition and coronary blood flow regulation mechanisms, but associations among SNPs of related genes and IHD are unclear.
Does the co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 genes protect against ischemic heart disease in patients undergoing coronary angiography?
Observational (n=468)
No
Does the co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 genes protect against ischemic heart disease in patients undergoing coronary angiography?
Odds Ratio: 0.185 (95% CI 0.44–0.77)
p-value: p=0.020
The co-presence of specific SNPs in the KCNJ11 and NOS3 genes may provide an independent protective effect against ischemic heart disease, highlighting a potential genetic role in coronary blood flow regulation.
Hypothesis-generating for CBF-related SNPs in IHD risk; larger validation studies needed before any clinical consideration.
Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (KATP) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the KATP channel that provides a potential protective effect against IHD.
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Severino et al. (2023) conducted an observational in Ischemic heart disease (n=468). Co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 vs. Absence of co-presence was evaluated on Ischemic heart disease (IHD) (OR 0.185, 95% CI 0.440-0.770, p=0.020). The co-presence of the genetic polymorphisms rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 was independently associated with a significantly lower risk of ischemic heart disease (OR 0.185).
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