FTO
Fat mass and obesity-associated protein
Gene Number: 79068
Location: 16q12.2
Key Functions: Energy balance regulation, appetite control, fat mass accumulation, obesity susceptibility
FTO encodes the fat mass and obesity-associated protein, a Fe²⁺/2-oxoglutarate–dependent dioxygenase that functions as an RNA demethylase. It specifically removes N⁶-methyladenosine (m⁶A) modifications from messenger RNA (mRNA), thereby influencing RNA stability, splicing, and translation. Through this epigenetic regulation of gene expression, FTO plays a pivotal role in controlling energy homeostasis, appetite regulation, and adipose tissue metabolism.
Polymorphisms within the FTO locus represent some of the most reproducible genetic markers associated with body mass index (BMI) and obesity risk across diverse populations. The A allele of rs9939609, in particular, is linked to increased food intake, preference for calorie-dense foods, reduced satiety, and higher susceptibility to weight gain. Carriers of risk alleles tend to display enhanced ghrelin signaling, contributing to greater hunger and decreased postprandial fullness.
Beyond adiposity, FTO variants influence glucose metabolism, insulin sensitivity, and risk for type 2 diabetes, largely through their effects on body composition and energy utilization. FTO expression is also responsive to environmental and behavioral factors — physical activity and dietary regulation can significantly mitigate the genetic predisposition to obesity, underscoring the dynamic interplay between genetic and environmental determinants of metabolism.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs1421085 | Analyze your DNA to see your genotype | C | Analyze your DNA to see a personalized result. |
rs9939609 | Analyze your DNA to see your genotype | A | Analyze your DNA to see a personalized result. |
rs1421085
TT – Common “risk-free” genotype; typical BMI and metabolic profile (R).
TC – Increased obesity risk and higher dietary fat intake (MUFA +2%, SAFA +1%) (R).
CC – Highest obesity risk; associated with lower thermogenic capacity in beige adipocytes, more meals/snacking, and elevated BMI/waist circumference (R).
Functional effect: The C allele disrupts a regulatory enhancer in intron 1, increasing expression of IRX3/IRX5 in adipocytes, shifting cell programming toward energy storage over thermogenesis and increasing hunger (R).
rs9939609
TT – Common genotype; baseline BMI and metabolic response (R).
TA – Each A allele adds ~0.26 kg/m² BMI (~750 g) and ~0.51 cm waist; increases hunger, fat intake, and meal frequency (R).
AA – Homozygous risk; strongest overall effect on adiposity and obesity risk (R).
Functional effect: The A allele increases food intake and snacking behaviors across populations, raising obesity risk substantially; physical activity can attenuate (~80% reduction) its BMI effect (R).
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