The association between APOA1 (rs5069) gene polymorphism and insulin resistance surrogates and metabolic indices among obese individuals with different glycemic statuses (euglycemic and T2DM)

Abstract

Obesity significantly contributes to insulin resistance and type 2 mellitus diabetes (T2DM), with both environmental and genetic factors influencing metabolic risk. Apolipoprotein A1 (APOA1), a key regulator of lipid metabolism, has genetic variants such as rs5069 that may affect metabolic profiles. This study investigated the association between APOA1 (rs5069) polymorphism and metabolic risk among euglycemic and T2DM obese individuals compared to healthy controls. Three hundred participants were enrolled and divided into healthy controls, euglycemic obese, and T2DM obese groups. Demographic, biochemical, and metabolic parameters including fasting blood sugar (FBS), HbA1c, lipid profile, HOMA-IR, TyG index, TyG-BMI, and METS-IR were assessed. APOA1 (rs5069) genotyping was conducted. Statistical analyses included ANOVA, chi-square tests, and principal component analysis (PCA). Obese individuals, particularly those with T2DM, showed significantly elevated insulin resistance markers, dyslipidemia, and metabolic indices (p < 0.001) compared to controls. The A allele of APOA1 (rs5069) was more frequent among obese participants. However, no significant differences in metabolic markers were observed among GG, GA, and AA genotypes within either obese group. PCA showed that metabolic variability was driven primarily by insulin resistance and lipid variables rather than genotype. While APOA1 (rs5069) genotype distribution varied across groups, it did not independently impact metabolic risk. Insulin resistance and dyslipidemia are the main contributors to metabolic disturbances in obesity, supporting the utility of non-invasive markers for early risk assessment.