The three genotypes CUBN rs2291521GA + AA, HNF1A rs55783344CT + TT, and LIPC rs17269397AA exhibited a synergistic effect in conjunction with FBS > 100 mg/dL (AOR = 3.792; 95% CI 2.330–6.170, AOR = 5.040; 95% CI 3.112–8.163, and AOR = 5.100; 95% CI 2.616–9.944, respectively), HDL-cholesterol male < 40 mg/dL, female < 30 mg/dL (AOR = 3.237; 95% CI 1.737–6.033, AOR = 2.809; 95% CI 1.554–5.078, and AOR = 2.551; 95% CI 1.389–4.684, respectively), and MetS (AOR = 5.974; 95% CI 3.626–9.840, AOR = 6.443; 95% CI 3.959–10.485, and AOR = 5.344; 95% CI 3.230–8.840, respectively). This evidence concerns the gene CUBN and metabolic syndrome.