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

Int J Obes (Lond). 2013 Jan;37(1):135-9. doi: 10.1038/ijo.2012.14. Epub 2012 Feb 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight / genetics*
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Germany / epidemiology
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / epidemiology
  • Obesity / genetics*
  • Pilot Projects
  • Proteins / genetics*
  • Triglycerides / blood
  • Weight Gain / genetics*
  • Weight Loss / genetics*

Substances

  • Blood Glucose
  • Proteins
  • Triglycerides
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human