Abstract Introduction Excessive weight is a significant risk factor for coronary artery disease (CAD), contributing to the development of cardiovascular events through complex metabolic and inflammatory mechanisms. While advancements have been made in understanding this relationship, the genetic basis underlying the link between excessive weight and CAD remains incomplete. Objective Evaluate which genetic polymorphisms are responsible for a higher probability of occurrence of CAD in patients with excessive weight and a few other traditional risk factors. Methods A case-control study was conducted involving individuals with excessive weight but with few of the other traditional risk factors as it is with low-density lipoprotein (LDL) levels 100 mg/dL, non-diabetic, and non-hypertensive. From 3157 individuals in our dataset, 202 (77.7% men; aged 51.0±8.5 years) were selected, comprising 120 patients with CAD (defined as having at least 70% stenosis in one major coronary artery) and 82 controls without CAD. Thirty-three genetic polymorphisms previously associated with CAD were genotyped using TaqMan real-time PCR. From these, five were selected not associated with the traditional risk factors: SLC30A8 rs1326634, PHACTR1 rs1332844, MTHFR rs1801131, APOE rs7412/rs429358 and TCF21 rs12190287. The bivariate analysis evaluated differences between genotypes, and after this, a multivariate logistic regression analysis showed which variants were significant and independently associated with CAD using the appropriate genetic model. Results SLC30A8, PHACTR1, MTHFR, APOE and TCF21 were significantly more prevalent in the CAD cohort. After multivariate logistic regression analysis of these five polymorphisms, three remained in the equation: PHACTR1 (OR=1.90; p=0.047), MTHFR (OR=6.28; p=0.021) on the recessive model and APOE (OR=2.66; p=0.011) on the dominant genetic model as independent and significantly associated with CAD risk in our population. Conclusion Obesity is a multifactorial disease with complex interactions among genes and environments. Our finding showed that three genetic variants (PHACTR1, MTHFR1298, and APOE) were associated with an increased risk of CAD in individuals with excessive weight and without other main CV risk factors. These genetic variants that influence inflammatory pathways and oxidative stress may interfere with overweight conditions, synergistically contributing to subclinical atherosclerosis and CAD.
Ferreira et al. (Sat,) studied this question.