Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a population at risk for type 2 diabetes.
OBJECTIVE
The impact of the diabetes risk gene transcription factor 7-like 2 (TCF7L2) on body weight is unclear. As TCF7L2 is expressed in adipose tissue and involved in Wnt-dependent regulation of adipogenesis, we studied the impact of TCF7L2 variants on body composition and weight loss during lifestyle intervention.


METHODS
We genotyped 309 German subjects at increased risk for type 2 diabetes for single nucleotide polymorphisms (SNPs) rs7903146, rs12255372, rs11196205, and rs7895340 in TCF7L2 and performed oral glucose tolerance tests before and after a 9-month lifestyle intervention. Fat distribution was quantified using whole-body magnetic resonance imaging/spectroscopy in a subgroup of 210 subjects.


RESULTS
After adjustment for confounding variables, we observed a negative impact of the type 2 diabetes allele of SNP rs7903146 on change in BMI (P = 0.0034) and on changes in nonvisceral (P = 0.0032) and visceral fat (P = 0.0165) during lifestyle intervention. An association of rs7903146 with lifestyle intervention-induced changes in insulin secretion, glucose concentrations, liver fat, or insulin sensitivity were not detected (all P > 0.2). Essentially the same results were obtained with SNP rs1255372. In contrast, we found no effects of SNPs rs11196205 and rs7895340 on change in BMI (all P > or = 0.5).


CONCLUSIONS
Our data reveal that diabetes-associated alleles of TCF7L2 are associated with less weight loss in response to lifestyle intervention. Thus, diabetes-associated TCF7L2 gene variation predicts the success of lifestyle intervention in terms of weight loss and determines individual susceptibility toward environmental factors.
Haupt
Axel
A
Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Thamer
Claus
C
Heni
Martin
M
Ketterer
Caroline
C
Machann
Jürgen
J
Schick
Fritz
F
Machicao
Fausto
F
Stefan
Norbert
N
Claussen
Claus D
CD
Häring
Hans-Ulrich
HU
Fritsche
Andreas
A
Staiger
Harald
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D001823:Body Composition / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D008019:Life Style; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D015431:Weight Loss / Q000235:genetics*; D055815:Young Adult
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein