Associations of SLC30A8 polymorphisms with metabolic and dietary parameters in a Brazilian obesity cohort

Obesity is a complex condition influenced by genetic and environmental factors. Beyond known appetite/satiety single nucleotide polymorphisms (SNPs), comprehensive genomic screening can reveal novel and clinically relevant associations. To investigate genetic associations of SNPs with anthropometric, biochemical, and dietary variables in a Brazilian obesity cohort. This cross-sectional study included 106 Brazilian individuals with obesity, categorized by severity (class I/II, n = 23; class III, n = 83). Anthropometric, body composition, biochemical, and dietary data were collected. Genotyping (Illumina®) analyzed approximately 640,000 SNPs. Associations were assessed via dominant/recessive genetic models, and a polygenic risk score (PRS) was constructed. No significant associations were found with classical appetite/satiety SNPs. However, comprehensive genomic screening identified two prevalent SLC30A8 SNPs (rs13266634, rs11558471). These SNPs were significantly associated with higher HDL cholesterol ( p < 0.05). Specific homozygous genotypes (CC for rs13266634, AA for rs11558471) linked to increased protein intake solely in class III obesity. The constructed PRS did not demonstrate predictive value for overall obesity risk (AUC = 0.520; p > 0.05). Our study unveils novel links between SLC30A8 variants and key metabolic (HDL-c) and dietary (protein intake) markers in obesity, contrasting with classical appetite-related SNPs. These findings suggest a broader, significant role for SLC30A8 in complex obesity phenotyping. The polygenic risk score was not predictive in this cohort. • Unveils novel associations of SLC30A8 gene polymorphisms with key metabolic (HDL cholesterol) and dietary (protein intake) parameters in individuals with obesity, expanding its known physiological relevance beyond type 2 diabetes. • Identifies a distinct composite genetic profile involving SLC30A8 homozygous genotypes that differentiates between obesity classes (I/II vs. III), offering a more nuanced understanding of obesity phenotypes. • Fills a critical gap in the literature by characterizing genetic predispositions to obesity and its metabolic complications in a highly admixed Brazilian cohort , moving beyond studies predominantly focused on European populations. • Elucidates functional interactions between SLC30A8 and pivotal obesity/diabetes genes ( FTO , TCF7L2 ), suggesting their involvement in a broader metabolic network and potential avenues for targeted interventions.