Lifestyle Genomics (Sep 2022)
The rs9939609 variant in FTO increases the risk of hypercholesterolemia in metabolically healthy subjects with excess weight
Abstract
Introduction: The fat mass and obesity-associated gene (FTO) is largely/primarely expressed in the hypothalamus. It plays a role in energy balance, regulation of food intake, and adipogenesis. According to metabolic phenotypes, studies have associated the FTO rs9939609 variant with body mass index (BMI), body fat mass, and dietary intake, but not with serum lipids. This study aimed to analyze the association of the FTO rs9939609 variant with serum lipids in Mexican adults with different metabolic phenotypes. Methods: We included 306 subjects aged 18-65 years, classified as normal weight (NW) or excess weight (EW) according to their BMI. EW included BMI from 25 to 39.9 kg/m2. Participants were classified into two metabolic phenotypes: metabolically healthy/metabolically unhealthy (MH/MUH). We use the homeostatic model assessment of insulin resistance and NCEP-ATP III cut-offs for glucose, triglycerides, high-density lipoprotein, and blood pressure. Subjects with ≥2 altered parameters were classified as MUH. The variant was determined by allelic discrimination with TaqMan® probes. Results: In subjects with the A-allele, significantly higher total cholesterol and low-density lipoprotein cholesterol were found (p<0.05). Furthermore, subjects with EW-MH and the AA or AT genotype had a significantly higher odds ratio for hypercholesterolemia (OR 4.48, 95% CI 1.48-13.59, p=0.008). Conclusion: The FTO rs9939609 variant may influence serum lipid concentrations, increasing the risk of hypercholesterolemia.