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Can the gene variant ZC3HC1 rs11556924 C>T increase Essential Hypertension risk? Influence of smoking in the relationship.
Session:
SESSÃO DE POSTERS 26 - CARDIOGENÉTICA EM AÇÃO!
Speaker:
Carolina Mendonça de Olim
Congress:
CPC 2025
Topic:
I. Hypertension
Theme:
27. Hypertension
Subtheme:
27.5 Hypertension – Prevention
Session Type:
Cartazes
FP Number:
---
Authors:
Carolina Olim; Maria Isabel Mendonça; Débora Sá; Francisco Sousa; Gonçalo Abreu; Matilde Ferreira; Eva Henriques; Sónia Freitas; Sofia Borges; Graça Guerra; Ana Célia Sousa; Roberto Palma Dos Reis
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Introduction</strong>: Essential Hypertension (EH) is a multifactorial disorder resulting from environmental and genetic factors and a primary factor for morbidity and mortality worldwide. A genetic variant in the ZC3HC1 gene, resulting in an arginine-to-histidine at the 363 position of the NIPA protein, has been associated with coronary artery disease (CAD). Still, its relationship with EH remains less clear.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Aim:</strong> Investigate whether ZC3HC1 rs11556924 C>T was associated with Essential Hypertension in a Portuguese Population without apparent CAD.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Methods:</strong> A prospective study included <span style="color:#010205">1421 participants from our Research Center dataset on a normal Portuguese population without apparent CAD.</span> Participants were followed during an extended period (average ± 7.0±5.7 years), and all demographic, biochemical, CV risk factors and clinical data were performed. ZC3HC1 rs11556924 was genotyped by TaqMan assays real-time polymerase chain reaction (PCR). The allelic and genotypic frequency distribution were estimated, and the Hardy-Weinberg equilibrium was tested. Data were displayed as absolute numbers, means and standard deviations (SD). The Student's t-test compared numerical variables, and the Chi-square was analyzed categorically. Multivariate logistic regression adjusted to confounders was performed. Statistical significance was defined as P <0.05, and all analyses were performed using SPSS statistical software, 25.0 version.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Results: </strong>The population was in the Hardy-Weinberg equilibrium either in the group with EH (p=0.438) or without EH (p=0.768). In the overall population, the frequencies of the CC, CT, and minor TT genotypes were, respectively, 38.4%, 48.2% and 13.4% in the EH group and 43.9%, 45.1% and 11.0% in the non-EH group (p=0.074). In bivariate analysis, the dominant model (TT+TC vs CC) presented an OR=1.255; p=0.031 and the recessive model (TT vs TC+CC) had an OR=1.249; p=0.162. The dominant model was also risk against EH in the non-smoking population, with statistical significance (p=0.016). In this population (non-smoking), after multivariate logistic regression adjusted for all other co-variables, ZC3HC1 also remained in the equation, with an OR=1.376 (CI: 1.047-1.809; p=0.022).</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif"">Conclusion: ZC3HC1 rs11556924 was shown to be a risk factor for essential hypertension. However, this variant may no longer be independently significant in the general population. Meanwhile, in non-smokers, this variant increases EA risk, either in bivariate or in multivariate model. Smoking, through vascular damage or inflammation pathways, can act as a confounder or modifier of EH in the general population. Removing smokers may reduce noise, unmasking the proper relationship between the variant and hypertension.</span></span></p>
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