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 <i>FTO</i> 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 <i>FTO</i> SNPs (<i>rs9939609</i>, <i>rs9940128</i>, and <i>rs8050136</i>) 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 <i>rs8050136</i> AA genotype was associated with a fourfold higher risk (aOR = 4.12; 95% CI: 1.49-11.95, <i>p</i> = 0.007). Smoking independently doubled AD risk (aOR = 2.33) and amplified the effect of <i>rs8050136</i>. 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. <i>FTO</i> polymorphisms, particularly <i>rs8050136</i> 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.