Atherogenic Dyslipidemia and Its Association with FTO Gene Polymorphisms in Working Perimenopausal Women

Atherogenic dyslipidemia (AD) is a high-risk phenotype for cardiovascular disease, characterized by elevated triglycerides, increased small dense low-density lipoprotein cholesterol (sdLDL-C), and frequently coexisting hypertension. Although FTO gene variants have been implicated in lipid dysregulation, their role in AD among Latin American women remains poorly defined. We conducted a case–control study in 219 working perimenopausal women (97 AD cases and 122 controls). Sociodemographic, clinical, and biochemical variables were assessed. Three FTO SNPs (rs9939609, rs9940128, and rs8050136) were genotyped. Associations were evaluated using logistic regression models adjusted for age and BMI, with gene–environment interactions tested for smoking. Linkage disequilibrium (LD) and haplotype analyses were also performed. Women with AD exhibited significantly higher triglycerides, LDL-C, and sdLDL-C, along with increased hypertension prevalence, but no differences in BMI or glycemia. Multivariable models identified LDL-C (aOR ≈ 8), triglycerides, sdLDL-C, and systolic blood pressure as the strongest determinants of AD. The rs8050136 AA genotype was associated with a fourfold higher risk (aOR = 4.12; 95% CI: 1.49–11.95, p = 0.007). Smoking independently doubled AD risk (aOR = 2.33) and amplified the effect of rs8050136. Adjusted haplotype analysis revealed that the A-A-A (aOR = 5.33; 95% CI: 1.42–20.00) and A-G-A combinations (aOR = 2.54; 95% CI: 1.01–6.38) were significantly associated with AD. FTO polymorphisms, particularly rs8050136 and the A-A-A and A-G-A haplotypes, contribute independently and supra-additively to AD risk. The observed gene–environment interaction with smoking emphasizes the multifactorial nature of AD and supports genotype-based risk stratification and targeted preventive strategies in precision cardiovascular medicine.