Polymorphism rs7214723 in CAMKK1: a new genetic variant associated with cardiovascular diseases.

Sofia Beghi,Francesca Cavaliere,Cesare Beghi,Annamaria Buschini,Matteo Manfredini,Claudio Corazzari,Sandro Ferrarese

doi:10.1042/bsr20210326

Sofia Beghi, Francesca Cavaliere + Show 5 more

Open Access

https://doi.org/10.1042/bsr20210326

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Journal: Bioscience reports	Publication Date: Jul 6, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: University of Parma, University of Insubria

Abstract

Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide. CVDs have a complex etiology due to the several factors underlying its development including environment, lifestyle, and genetics. Given the role of calcium signal transduction in several CVDs, we investigated via PCR-restriction fragment length polymorphism (RFLP) the single nucleotide polymorphism (SNP) rs7214723 within the calcium/calmodulin-dependent kinase kinase 1 (CAMKK1) gene coding for the Ca2+/calmodulin-dependent protein kinase kinase I. The variant rs7214723 causes E375G substitution within the kinase domain of CAMKK1. A cross-sectional study was conducted on 300 cardiac patients. RFLP-PCR technique was applied, and statistical analysis was performed to evaluate genotypic and allelic frequencies and to identify an association between SNP and risk of developing specific CVD. Genotype and allele frequencies for rs7214723 were statistically different between cardiopathic and several European reference populations. A logistic regression analysis adjusted for gender, age, diabetes, hypertension, BMI and previous history of malignancy was applied on cardiopathic genotypic data and no association was found between rs7214723 polymorphism and risk of developing specific coronary artery disease (CAD) and aortic stenosis (AS). These results suggest the potential role of rs7214723 in CVD susceptibility as a possible genetic biomarker.

Highlights

Cardiovascular diseases (CVDs) are the leading cause of deaths in industrialized countries affecting increasing number of people every year [1]
Polymorphisms have been shown to have important roles as biomarkers for the prognosis and diagnosis of diseases, health prevention, epidemiology, and pharmacology [28]
The identification and study of genetic variants involved in multifactorial diseases is important given the complexity of their underlying genetic architecture

Summary

Introduction

Cardiovascular diseases (CVDs) are the leading cause of deaths in industrialized countries affecting increasing number of people every year [1]. CVDs refer to a wide range of conditions affecting heart function and blood vessels, two of the most frequent being coronary artery disease (CAD) and aortic stenosis (AS). CAD results from progressive stenosis of coronary arteries caused by the atherosclerosis process. Clinical syndromes are caused by an imbalance between oxygen supply and demand, resulting in a myocardial perfusion inadequate to meet metabolic demand (ischemia). AS results from complex and non-completely understood pathophysiologic mechanisms, causing thickening, calcification, and/or fusion of the aortic valve leaflets (LV), determining a variable degree of stenosis in the left ventricle outflow tract [2]

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