Association of FTO rs9939609 Polymorphism With Obesity and Elevated Glycemic Parameters in a Syrian Population: A Case–Control Study

BACKGROUND: Obesity is a major risk factor for Type 2 diabetes mellitus (T2DM), with substantial genetic determinants. The fat mass and obesity-associated (FTO) gene rs9939609 polymorphism has been consistently associated with obesity risk across diverse populations. This case-control study is aimed at investigating FTO rs9939609 and its associations with obesity risk and glycemic parameters in a Syrian population for the first time. METHODS: A total of 97 participants (50 obese cases and 47 nonobese controls) were recruited from two university hospitals in Damascus, Syria. Among obese participants, 25 had T2DM, including 11 newly diagnosed, treatment-naïve patients. Genotyping was performed using PCR-RFLP, and associations were assessed using logistic and linear regression analyses. RESULTS: The minor allele frequency was significantly higher in obese cases compared to controls (36.0% vs. 20.21%, p = 0.015). Under the dominant genetic model, risk allele carriers exhibited a 3.76-fold increased obesity risk (95% CI: 1.62-8.74, p = 0.002). This association was preserved when the analysis was restricted to nondiabetic obese participants. No significant associations were observed between genotypes and anthropometric parameters within the obese group. Among obese nondiabetic individuals, A-allele carriers showed significantly elevated fasting blood glucose (p = 0.004) and HbA1c levels (p = 0.034) compared to TT homozygotes; these associations remained significant after adjusting for BMI, WC, and WHR in separate models. A pooled analysis of all obese T2DM patients (n = 25) revealed significantly higher HbA1c in A-allele carriers (p = 0.027), with exploratory subgroup analyses suggesting a stronger association in treatment-naïve patients, though these findings require confirmation in larger studies. CONCLUSIONS: Our study provides the first evidence that FTO rs9939609 is significantly associated with obesity risk in the Syrian population and may contribute to early glycemic dysregulation in genetically susceptible obese individuals. Subgroup findings warrant validation in larger cohorts.