Genetic factors play an important role in metabolic disease susceptibility. Apolipoproteins E (APOE) and A1 (APOA1) are key regulators of lipid metabolism and have been individually associated with dy Show more
Genetic factors play an important role in metabolic disease susceptibility. Apolipoproteins E (APOE) and A1 (APOA1) are key regulators of lipid metabolism and have been individually associated with dyslipidemia and type 2 diabetes mellitus (T2DM). This study aimed to examine the individual and combined associations of APOE (rs429358, rs7412) and APOA1 (rs5069) gene polymorphisms with obesity and T2DM. A case-control study was conducted including 350 participants categorized into four groups: controls (n = 100), euglycemic obese individuals (n = 100), obese individuals with T2DM (n = 100), and non-obese individuals with T2DM (n = 50). Biochemical parameters, including lipid profiles and glycemic indices, were assessed. Genotyping was performed using TaqMan Metabolic disturbances and dyslipidemia were observed across all patient groups, with the most pronounced abnormalities in obese individuals with T2DM. The APOE ε4 allele and ε4/ε4 genotype were significantly associated with obese T2DM compared with controls and euglycemic obese subjects. The APOA1 rs5069 A allele and AA genotype were associated with both obesity and T2DM. Spearman correlation analysis revealed a positive co-occurrence of APOE and APOA1 genotypes in euglycemic obese (ρ = 0.264, p = 0.008) and obese T2DM (ρ = 0.347, p < 0.001) groups, but not in non-obese T2DM individuals. However, in multivariate logistic regression models adjusted for age, sex, and BMI, the APOE × APOA1 interaction term did not reach statistical significance (p = 0.138). APOE ε4 and APOA1 rs5069 A alleles were independently associated with obesity-related T2DM. Although these variants demonstrated correlated distribution patterns in obese individuals, the formal gene-gene interaction on T2DM risk was not statistically significant after multivariable adjustment. These findings suggest that obesity may represent a metabolic context in which combined genetic associations are more evident, warranting further investigation in larger and well-powered cohorts. Show less