Coronary artery disease in smokers with low traditional risk burden

Background/objectives: Coronary arterial disease (CAD) poses a significant public health challenge, with tobacco as the most predominant modifiable risk factor in young individuals. Despite a strong correlation between tobacco use and CAD, many smokers remain CAD-free. This fact raises questions about the complex interplay between environmental and genetic factors that contribute to CAD. Objective: Identify genetic polymorphisms that may be responsible for CAD in smokers without the main cardiovascular risk factors. Methods: A small retrospective case-control association study included current smokers aged 35–50 with low-density lipoprotein (LDL) levels <100 mg/dL who were non-diabetic and non-hypertensive. A total of 134 individuals (83% male; mean age of 48.9 ± 8.4 years) were selected from the GENEMACOR population: 97 CAD patients defined as having at least 70% stenosis in one major coronary artery, and 37 controls without CAD. Nine genetic variants from 8 genes previously associated with CAD but not with traditional risk factors (TRFs) were genotyped using TaqMan real-time PCR: CDKN2B-AS1, TCF21, PHACTR1, MIA3, ADAMTS7, ZC3HC1, SMAD3, and GJA4. Bivariate analyses compared genotypic proportions between CAD and non-CAD groups, reporting odds ratios (ORs) and confidence intervals (CIs). Multivariate logistic regression evaluates variables independently associated with CAD. The Hardy-Weinberg equilibrium was tested. Results: The intronic PHACTR1 polymorphism rs12526453 C > T was significantly more prevalent in cases, with the dominant model presenting 86.6% in CAD smokers and 70.3% in non-CAD smokers (OR = 2.73; p = 0.028). After logistic regression, which included significant variables in the bivariate analysis, PHACTR1 rs12526453 remained in the model (OR = 3.02; p = 0.038), along with dyslipidemia (OR = 3.58; p = 0.004), obesity (OR = 4.39; p = 0.031), and a family history of CAD (OR = 5.56; p = 0.031). Conclusions: Our findings show that the PHACTR1 T allele is associated with an increased risk of CAD in smokers with a family history, dyslipidemia and obesity, in the absence of other major cardiovascular risk factors. These results support the concept that genetic susceptibility may modulate the vascular response to chronic inflammatory and oxidative stress. Further prospective and functional studies are warranted to clarify the underlying biological mechanisms and the potential clinical value of integrating genetic profiling into personalised cardiovascular risk stratification.

Descrição

Palavras-chave

Coronary artery disease Genetic variants Smoking Dentistry (miscellaneous) Cardiology and Cardiovascular Medicine

URI

http://hdl.handle.net/10362/204491

DOI

10.1016/j.jmccpl.2026.100855

Coleções

NMS - Artigos em revista internacional com arbitragem científica

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