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.


METHODS
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)).


METHODS
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).


CONCLUSIONS
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.
Department of Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
A
A
Woehning
J-H
JH
Schultz
E
E
Roeder
A
A
Moeltner
B
B
Isermann
P P
PP
Nawroth
C
C
Wolfrum
G
G
Rudofsky
D000293:Adolescent; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D010865:Pilot Projects; D011506:Proteins / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics*
D001786:Blood Glucose; D011506:Proteins; D014280:Triglycerides; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human