Polymorphism of FTO rs1421085 as risk of metabolic syndrome; case-control study in two ethnics, Javanese and Malay population, Indonesia

Background: Metabolic syndrome (MetS) represents a complex interplay between genetic predisposition, adiposity, and lifestyle determinants. The fat mass and obesity-associated (FTO) gene variant rs1421085 has been linked to obesity and metabolic disturbances; however, evidence from Indonesia, a country with diverse ethnic and dietary backgrounds remains limited. This study investigated the association between FTO rs1421085 polymorphism and MetS among Javanese and Malay adults. Methods: A matched case control study of 256 adults (120 Javanese and 136 Malay) aged 20-60 years was conducted. MetS was diagnosed using modified NCEP ATP III criteria. Genotyping was performed by PCR-RFLP and Tetra-ARMS PCR. Logistic regression under additive, dominant, and recessive models was adjusted for age, sex, ethnicity, BMI, and dietary intake. Results: In the overall population, the FTO rs1421085 CC genotype was associated with higher MetS risk, but the association attenuated after adjustment for BMI and dietary intake. Interestingly, this association persisted in men. Among older Malay participants, the TC genotype also increased MetS risk, which diminished after dietary adjustment. Conclusions: These findings suggest that the FTO rs1421085 variant may influence MetS susceptibility partly through adiposity- and nutrigenetic mechanisms, with effects modified by sex, age, and ethnicity. Future larger and integrative studies incorporating multigenic, lifestyle, and sociodemographic factors are warranted to confirm and extend these observations. © The Author(s) 2025.