The A-allele of the common FTO gene variant rs9939609 complicates weight maintenance in severe obese patients

OBJECTIVE: The A-allele of the fat mass and obesity-associated (FTO) gene variant rs9939609 has been associated with increased body weight, whereas no effect on weight loss during weight reduction programs has been observed. We questioned whether the AA-genotype interferes with weight stabilization after weight loss. DESIGN: We conducted a monocentric, longitudinal study involving obese individuals. The FTO gene variant rs9939609 was genotyped in participants attending a weight reduction program that was divided into two phases: a weight reduction period with formula diet (12 weeks) and a weight maintenance phase (40 weeks). Body weight, body mass index (BMI), blood pressure and concentrations of blood glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides were determined in week 0 (T-0), after 12 weeks (T-1) and at the end in week 52 (T-2). SUBJECTS: A total of 193 obese subjects aged between 18 and 72 years (129 female, 64 male; initial body weight: 122.4 +/- 22.3 kg, initial BMI: 41.8 +/- 6.7 kg m(-2)) were included. RESULTS: Genotyping revealed 32.1% TT-, 39.4% AT- and 28.5% AA-genotype carriers. At T-0, carriers of the AA-genotype had significantly higher body weight (P = 0.04) and BMI (P = 0.005) than carriers of the TT-genotype. Of the 193 participants, 68 discontinued and 125 completed the program. Dropout rate was not influenced by genotype (P = 0.33). Completers with AA-genotype showed significantly lower additional weight loss during the weight maintenance phase than TT-genotype carriers (P = 0.02). Furthermore, among participants facing weight regain during weight maintenance (n = 52), more subjects were carrying the AA-genotype (P = 0.006). No influence of genotype on weight reduction under formula diet was observed (P = 0.32). CONCLUSION: In this program, the AA-genotype of rs9939609 was associated with a higher initial body weight and did influence success of weight stabilization. Thus, emphasizing the maintenance phase during a weight reduction program might result in better success for AA-genotype carriers. International Journal of Obesity (2013) 37, 135-139; doi: 10.1038/ijo.2012.14; published online 7 February 2012