Variants within the FTO gene are important determinants of body mass index (BMI), but their role in determination of BMI changes after combined dietary/physical activity intervention is unclear. We have analyzed 107 unrelated overweight non-diabetic Czech females (BMI over 27.5 kg/m(2), age 49.2+/-12.3 years). FTO variants rs17817449 (first intron) and rs17818902 (third intron) were genotyped. The life style modification program (10 weeks) consisted of an age-matched reduction of energy intake and exercise program (aerobic exercise 4 times a week, 60 min each). The mean BMI before intervention was 32.8+/-4.2 kg/m(2) and the mean achieved weight loss was 4.8+/-3.5 kg (5.3+/-3.5 %, max. -15.5 kg, min. +2.0 kg, p<0.01). No significant association between BMI decrease and FTO variants was found. Also waist-to-hip ratio, body composition (body fat, water, active tissue), lipid parameters (total, LDL and HDL cholesterol, triglycerides) glucose and hsCRP changes were independent on FTO variants. FTO variants rs17817449 and rs17818902 are not associated with BMI changes after combined short time dietary/physical activity intervention in overweight females.