Association of APOA5 rs3135506 and CETP rs708272 Polymorphisms with Metabolic Syndrome in a Moroccan Population

Background: Metabolic syndrome (MetS) is a multifactorial condition and a major public health concern due to its strong association with cardiovascular disease and type 2 diabetes. Genetic factors contribute to its development. This study aims to evaluate the association between polymorphisms in genes APOA5 and CETP and susceptibility to MetS and its components in a Moroccan population. Methods: A case–control study was conducted, including 136 MetS patients and 138 controls recruited from the Doukkala region (Morocco). The APOA5 rs3135506 (C>G) and CETP rs708272 (G>A) polymorphisms were genotyped using PCR-RFLP. Results: The APOA5 rs3135506 polymorphism was significantly associated with increased MetS risk. The CG and GG genotypes conferred 2.39-fold (OR = 2.39; p = 0.0008) and 7.17-fold (OR = 7.17; p = 0.0007) higher risks, respectively, with significant associations also observed under dominant (OR = 2.76; p < 0.0001), recessive (OR = 4.79; p = 0.006), and allelic (OR = 2.36; p < 0.0001) models. The GG genotype was also associated with general and abdominal obesity, hypertension, and hyperglycemia, whereas the CG genotype was associated with dyslipidemia. For CETP rs708272, the AA genotype was associated with increased MetS risk (OR = 3.31; p = 0.0078), with significant associations under dominant (OR = 1.81; p = 0.0160), recessive (OR = 2.80; p = 0.0185), and allelic (OR = 1.81; p = 0.0023) models. However, these associations were no longer significant after adjustment for age and sex. Combined genotype analysis revealed increased MetS risk for the CG–GG, CG–GA, and GG–AA combinations (OR = 4.64, 2.98, and 7.35, respectively). Conclusion: The APOA5 rs3135506 and CETP rs708272 polymorphisms may contribute to MetS susceptibility in the Moroccan population, with certain combined genotypes associated with increased risk. These findings support their potential as genetic biomarkers for early risk assessment but require confirmation in larger studies.