Association of apolipoprotein A1 (rs 5069) genotyping with 25-hydroxyvitamin D deficiency and insulin resistance as a metabolic and genetic difference in obesity and type 2 diabetes mellitus

Abstract

Obesity and type 2 diabetes mellitus (T2DM) are significant issues for public health, frequently occurring together with vitamin D deficiency and metabolic diseases. This study aimed to investigate whether the APOA1 single nucleotide polymorphism rs5069 is associated with 25-hydroxyvitamin D (25[OH]D) deficiency and insulin-resistance–related traits in Egyptian adults. In this cross-sectional study, 350 Egyptian adults (age 35–55 years) were grouped as: (1) obese non-diabetic (n = 100), (2) obese with T2DM (n = 100), (3) non-obese with T2DM (BMI < 30, n = 50), and (4) controls (BMI < 30 and 25[OH]D ≥ 20 ng/mL, n = 100). We measured BMI, 25(OH)D, FBS, HbA1c, fasting insulin, HOMA-IR and lipid profile. APOA1 rs5069 genotypes were determined by TaqMan assays. Group comparisons, Pearson correlation, and multivariate logistic regression (three models with incremental adjustments) were performed. Vitamin D deficiency (25[OH]D < 20 ng/mL) was common in obese and diabetic groups (p < 0.001). Obese participants with T2DM had the worst metabolic profile (higher FBS, HbA1c, fasting insulin and HOMA-IR; dyslipidemia). The AA genotype and A allele of rs5069 were more frequent in obesity and T2DM than controls (genotype p = 0.005–0.011; allele p = 0.002–0.005). In obese groups, higher 25(OH)D levels were independently associated with lower odds of carrying GA and AA genotypes versus GG after adjustment for glycemic and lipid variables (models 2 and 3). No significant genotype–vitamin D association was observed in non-obese T2DM. APOA1 rs5069 (AA genotype) is associated with obesity and T2DM in this Egyptian cohort. Higher 25(OH)D was associated with reduced odds of GA/AA genotypes in obese participants, suggesting an interaction between vitamin D status and APOA1-related genetic susceptibility. Further longitudinal and mechanistic studies are needed.