Association between the FTO gene variant rs9939609 and obesity risk: A case-control study

Obesity is a major global health problem, driven by complex interactions between genetic, environmental, and lifestyle. The Fat Mass and Obesity-Associated ( FTO ) gene, located on chromosome 16q12.2, has been identified through genome-wide association studies (GWAS) as a key genetic determinant of obesity risk. This study aimed to investigate the association between the FTO rs9939609 variant and obesity, defined by body mass index (BMI) and waist circumference, in the Indonesian population. A case–control study was conducted among 294 adults aged 19–59 years, consisting of 93 non-obese controls (BMI 18.5–24.9 kg/m 2 ) and 201 obese cases (BMI ≥25.0kg/m 2 ). Genotyping for FTO rs9939609 was performed using the TaqMan Allelic Discrimination Assay. Anthropometric measurements included body weight, height, and waist circumference. Food intake was evaluated using a semi-quantitative food frequency questionnaire (SQ-FFQ) and three 24-hour food recalls, while physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). Following multiple regression analyses after adjustment for the age, gender, activity, and food intake, AA genotype of the FTO polymorphism was strongly associated with obesity as per the BMI in both co-dominant model (aOR: 3.63, 95% CI: 1.36–9.67, p = 0.01) and recessive model (aOR: 3.75, 95% CI: 1.47–9.62, p < 0.01). Similarly, as assessed by waist circumference, the AA genotype was associated with increased risk of obesity in both the co-dominant (aOR: 3.05, 95% CI: 1.21–7.69, p = 0.02) and recessive (aOR: 3.03, 95% CI: 1.25–7.34, p = 0.01) models. The FTO rs9939609 AA genotype is significantly associated with increased risk of both general and central obesity in the Indonesian population. Larger, longitudinal studies incorporating additional genetic, metabolic, and lifestyle factors are warranted to confirm these findings and further explore their potential relevance for obesity risk assessment. • In a codominant model, the AA genotype of FTO rs9939609 is strongly linked to a higher obesity risk in Indonesians. • Obesity is not purely genetic; age, sex, low physical activity, and excess food intake are key predictors.