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Does the LPA genotype have a role in coronary artery disease risk beyond lipoprotein(a) values?
Session:
Comunicações Orais - Sessão 07 - Genética em Cardiologia
Speaker:
Ana Débora Câmara de Sá
Congress:
CPC 2024
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.6 Basic Science - Other
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Ana Débora Câmara De Sá; M.I. Mendonça; F. Sousa; E. Henriques; S. Freitas; M. Rodrigues; S. Borges; G. Guerra; G. Abreu; A. Drumond; A.C. Sousa; R. Palma Dos Reis
Abstract
<p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Introduction: </strong>High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for coronary artery disease (CAD). Many functional single nucleotide polymorphisms (SNPs) of the LPA gene have pronounced effects on Lp(a) concentrations; studies show that rs3798220 polymorphism is strongly associated with Lp(a) concentration and also with risk of CAD.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Goal:</strong> To evaluate if LPA rs3798220 T>C is associated with CAD beyond its effect on Lp(a) levels. </span></span></p> <p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Methods: </strong>We performed a case-control study with 3,157 individuals (1,721 CAD patents and 1,436 controls). The LPA rs3798220 T>C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). <span style="background-color:white"><span style="color:#212529">This variant has a minor allele frequency (MAF) <2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis.</span></span> Laboratory analysis was performed, and Lp(a) biochemical levels were measured in the cases and controls. Chi-squared tests were used to determine differences by genotype in CAD association (in cases and controls). We also reported a multivariate logistic regression to test if this LPA variant is still independently associated with CAD after adjustment to Lp(a) levels and traditional risk factors for CAD.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Results: </strong>Wild-type genotype TT was increased in the group without CAD, whereas the genotype TC was higher in patients with CAD (p<0.0001). After multivariate logistic regression, adjusted for traditional risk factors, the TC genotype remained in the equation as an independent risk factor for CAD (OR=2.36; 95%CI: 1.54–3.61; p<0.0001). When the multivariate regression analysis is adjusted for traditional risk factors plus Lp(a) levels, the TC genotype remains in the equation as independently associated with CAD despite being substantially attenuated (OR=1.67; 95%CI: 1.07–2.60; p=0.025).</span></span></p> <p><strong><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">Conclusion: </span></span></strong><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">LPA rs3798220 T>C may be an independent risk factor for CAD beyond the effect of rising Lp(a) levels. Perhaps </span></span><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">testing for the genetic determinants of Lp(a) relative to direct measurement of Lp(a) level could provide additional prognostic utility. </span></span></p>
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