Association of Obesity-Related Genetic Variants with Android Fat Patterning and Cardiometabolic Risk in Women

<b>Background/Objectives:</b> The location and distribution of excess fat, rather than overall adiposity, are stronger predictors of cardiometabolic risk and are commonly assessed using the waist-to-hip ratio (WHR). Fat distribution in women has a heritable component, yet the genetic factors that influence it remain poorly understood. We aim to assess the association between obesity-related polymorphisms with WHR and cardiometabolic risk in overweight and obese women. <b>Methods:</b> A cohort study was conducted in 512 women (56.1 ± 6.4 years; body mass index (BMI) ≥ 25 kg/m²). WHR was calculated, and participants were classified into android (WHR > 0.85) or gynoid (WHR ≤ 0.85) obesity groups. We genotyped 15 SNPs previously associated with obesity using TaqMan real-time PCR. Different genetic models (dominant, recessive, and allelic) were analysed, and bivariate and multivariate analyses were performed to compare the fat distribution groups. <b>Results:</b> Of the 15 SNPs studied, only 3 presented a significant association with WHR > 0.85. <i>PSRC1</i> rs599839 in a dominant model (AA + GA vs. GG) with OR = 3.18 (<i>p</i> = 0.041), <i>SLC30A8</i> rs1326634 in a recessive model (CC vs. TC + TT) (OR = 2.38; <i>p</i> = 0.004), both showing increased susceptibility to central obesity. <i>KIF6</i> rs20455 offers protection in a recessive model (CC vs. TC + TT) with an OR of 0.47 (<i>p</i> = 0.043). After adjusted multivariate analysis, only <i>SLC30A8</i> and diabetes remained independently associated with an increased risk of android obesity (OR = 2.50; <i>p</i> = 0.003 and OR = 3.63; <i>p</i> = 0.004, respectively). <b>Conclusions</b>: The <i>SLC30A8</i> variant was significantly associated with android fat distribution and high cardiometabolic risk in overweight/obese women. Identifying genetic factors that influence fat distribution may help specify targeted lifestyle changes or pharmacological interventions to reduce risk.