Our study, exploring the hypothesis that overweight and severe-obese individuals, who carry more than three LH cholesterol CYP27A1 variants (rs4674345 A, rs1554622 A, and rs4674338 G; LH: 3–6 group), are more likely to present higher CVD risk factors and premature biological aging, founds that LTL attrition and insulin resistance were significant higher in severe-obese-LH: 3–6 than severe-obese-LH: 0–2, while insulin resistance was also greater in overweight-LH: 3–6 compared with overweight-LH: 0–2. Here, CYP27A1 is linked to Insulin resistance.