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ZNF 259C>G variant rs964184 is associated with Coronary artery disease and dyslipidemia in the younger population
Session:
Posters (Sessão 2 - Écran 3) - Ciência Básica
Speaker:
M. Raquel Santos
Congress:
CPC 2022
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.3 Basic Science - Cardiac Diseases
Session Type:
Pósters Electrónicos
FP Number:
---
Authors:
m. Raquel Santos; Maria Isabel Mendonça; Débora sá; Margarida Temtem; Ana Célia Sousa; Eva Henriques; Mariana Rodrigues; Sónia Freitas; Sofia Borges; Graça Guerra; Ana Freitas; Ilídio Ornelas; António Drumond; Roberto Palma Dos Reis
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><span style="font-size:12.0pt">GWAS demonstrates that BUD13-ZNF259 rs964184 polymorphism was associated with susceptibility to coronary artery disease (CAD). CAD is a dynamic inflammatory disease caused by atherosclerosis, and BUD13-ZNF259 encodes ZPR1 protein that interacts with tyrosine kinase receptors. Recent research has shown that spleen tyrosine kinase (Syk) interact with ZPR1 at the cellular level, increasing inflammatory response and atherogenesis with plaque development in mice.</span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong><span style="font-size:12.0pt">Aim:</span></strong><span style="font-size:12.0pt"> Evaluate the association of BUD13-ZNF259 rs964184 polymorphism with CAD and dyslipidemia (a critical risk factor to CAD).</span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong><span style="font-size:12.0pt">Methods:</span></strong><span style="font-size:12.0pt"> A case-control study with 3,160 individuals (1,723 CAD patients with a mean age of 53.3</span><span style="font-size:12.0pt">±</span><span style="font-size:12.0pt">7.9 years; 78.7% male and 1437 controls, mean age 52.8</span><span style="font-size:12.0pt">±</span><span style="font-size:12.0pt">7.8; 76.3% male. Participants were stratified into two different age groups (<45 and >55 years). BUD13-ZNF259 rs964184 variant was genotyped and analysed using the dominant model (CG+GG) vs CC. Bivariate analysis and multivariate logistic regression were performed in the two age groups to investigate whether BUD13-ZNF259 rs964184 polymorphism was associated with CAD susceptibility and dyslipidemia.</span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong><span style="font-size:12.0pt">Results: </span></strong><span style="font-size:12.0pt">After bivariate analysis, the group <45 years, the CG+GG genotype of the BUD13-ZNF259 rs964184 showed association with CAD and dyslipidemia, with an OR=1.46 (p=0.036) and OR=1.85 (p=0.003), respectively. In the >55 years group, this genetic model was associated with dyslipidemia with an OR=1.46 (p=0.020) but not with CAD. After multivariate logistic regression, the CG+GG genotype was an Independent risk factor for CAD susceptibility only in the younger population (OR=1.60; p=0.037). </span></span></span></p> <p><strong><span style="font-size:12.0pt"><span style="font-family:"Calibri","sans-serif"">Conclusion:</span></span></strong><span style="font-size:12.0pt"><span style="font-family:"Calibri","sans-serif""> BUD13-ZNF259 rs964184 polymorphism is a risk factor for dyslipidemia and CAD onset, only in the young population. The interaction of the ZPR1 with Syk at the cellular level seems to be more relevant in young patients. Our results suggest that the BUD13-ZNF259 rs964184 variant may represent a possible prophylactic and therapeutic target in the future, particularly in young CAD patients.</span></span></p>
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