The rs9939609 Variant in FTO Increases the Risk of Hypercholesterolemia in Metabolically Healthy Subjects with Excess Weight

Abstract

<b><i>Introduction:</i></b> The fat mass and obesity-associated gene (<i>FTO</i>) is largely/primarily 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 <i>FTO</i> 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 <i>FTO</i> rs9939609 variant with serum lipids in Mexican adults with different metabolic phenotypes. <b><i>Methods:</i></b> We included 306 subjects aged 18–65 years, classified as normal weight 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 cutoffs 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. <b><i>Results:</i></b> In subjects with the A allele, significantly higher total cholesterol and low-density-lipoprotein cholesterol were found (<i>p</i> &#x3c; 0.05). Furthermore, subjects with EW-MH and the AA or AT genotype had a significantly higher odds ratio for hypercholesterolemia (odds ratio 4.48, 95% confidence interval: 1.48–13.59, <i>p</i> = 0.008). <b><i>Conclusion:</i></b> The <i>FTO</i> rs9939609 variant may influence serum lipid concentrations, increasing the risk of hypercholesterolemia.