Association Between Fto Gene and Metabolic Syndrome Severity: The Role of Sedentary Behaviour and Skeletal Muscle in Transitioning Rural Populations of Assam, Northeast India.

Objective: Metabolic syndrome (MetS) is the clustering of metabolic risk factors, including increased adiposity, high blood pressure, high blood glucose level, or abnormal lipid profile. The present study aims at understanding the association between the FTO gene (rs9939609) polymorphism and MetS among two rural population groups of Assam, Northeast India. Further, the study aims to investigate the moderating role of sedentary behaviour in the association between the FTO risk allele and MetS severity. Lastly, the study investigates the mediating role of skeletal muscle index in the association between sedentary behaviour and MetS severity. Design and method: A cross-sectional study was conducted among unrelated adult individuals of the Mising and Ahom communities of Dhemaji district, Assam, Northeast India. Genotyping for the FTO gene's rs9939609 polymorphism was performed on a subset. Multiple regression analysis was conducted to determine the genetic, socio-demographic, lifestyle, and body composition determinants of MetS (Joint Harmonised Definition). To understand the gene-environment interaction, Univariate Analysis of Variance was employed. To understand how sedentary behaviour impacts the MetS severity score, the role of Skeletal Muscle Index was examined through linear regression and mediation analysis. All statistical analyses were performed using IBM SPSS Statistics 26. Results: Regression analysis revealed that the odds of having MetS were eight times higher among individuals carrying the FTO rs9939609 risk allele, after adjusting for all the socio-demographic, lifestyle, and body composition measures. Univariate Analysis of Variance revealed that the FTO rs9939609 risk allele impacts the MetS severity score through its interaction with sedentary behaviour. Linear regression and mediation analysis revealed a mediating effect of Skeletal Muscle Index on the impact of sedentary behaviour on MetS Severity. Conclusions: The FTO gene rs9939609 risk allele significantly increases the odds of developing MetS among the rural population of Assam, Northeast India. The effect of the risk allele is exacerbated by sedentary behaviour. Further, the mediating role of skeletal muscle highlights the need for interventions targeting the improvement of muscle mass among individuals carrying the risk allele.