PMID- 18546086
OWN - NLM
STAT- MEDLINE
DCOM- 20081114
LR  - 20101118
IS  - 0018-5043 (Print)
IS  - 0018-5043 (Linking)
VI  - 40
IP  - 10
DP  - 2008 Oct
TI  - TCF7L2 polymorphism rs7903146 and predisposition for type 2 diabetes mellitus in 
      obese children.
PG  - 713-7
LID - 10.1055/s-2008-1078720 [doi]
AB  - Polymorphism RS7903146 in transcription factor 7-like2 gene ( TCF7L2) is 
      associated with type 2-diabetes mellitus (T2DM) in adults. Concerned with 
      predisposition for diabetes mellitus in obese children, we tested if risk 
      genotypes TC and TT of rs7903146 are more common in obese children with increased 
      homeostasis model assessment insulin resistance index (HOMA-IR) compared to obese 
      controls with normal HOMA-IR. As exploratory analysis, we also calculated 
      beta-cell function for these risk genotypes and measured glucagon-like peptide 1 
      (GLP-1) in a subgroup. The cohort was 401 obese children (BMI > 2SDS; 211 female; 
      59% presenting increased HOMA-IR) from two German outpatient obesity referral 
      centers. Genotype distributions in patients presenting increased HOMA-IR (TT: 
      10.18%, CT: 35.65%, CC: 54.17%) and in patients with normal HOMA-IR (TT: 8.66%, 
      CT: 42.67%, CC: 48.67%) provided no significant effect of these two risk 
      genotypes (p > 0.2). Correction for possible confounder's gender, age, pubertal 
      stage, and BMI revealed no association with glucose metabolism parameters 
      including GLP-1. However, exploratory HOMA-B% index was comparatively higher in 
      TT-homozygotes (p=0.021) as compared to CC-homozygotes. We conclude that even 
      though TT and CT genotypes were not higher in patients presenting elevated 
      HOMA-IR, the higher HOMA-B% index in TT-homozygotes indicates TCF7L2 to be a 
      susceptibility gene for the development of impaired glucose tolerance in obese 
      children as demonstrated in several adult cohort studies.
FAU - Roth, C L
AU  - Roth CL
AD  - Paediatric Endocrinology, Seattle Children's Hospital Research Institute, 1900 
      Ninth Avenue, Seattle, WA 98101, USA. christian.roth@seattlechildrens.org
FAU - Hinney, A
AU  - Hinney A
FAU - Reinehr, T
AU  - Reinehr T
FAU - Schreiner, F
AU  - Schreiner F
FAU - Nguyen, T T
AU  - Nguyen TT
FAU - Muller, T
AU  - Muller T
FAU - Scholl, C
AU  - Scholl C
FAU - Woelfle, J
AU  - Woelfle J
FAU - Karpushova, A
AU  - Karpushova A
FAU - Schafer, H
AU  - Schafer H
FAU - Nothen, M M
AU  - Nothen MM
FAU - Hebebrand, J
AU  - Hebebrand J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080610
PL  - Germany
TA  - Horm Metab Res
JT  - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et 
      metabolisme
JID - 0177722
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
SB  - IM
MH  - Body Mass Index
MH  - Child
MH  - Diabetes Mellitus, Type 2/*complications/*genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Male
MH  - Obesity/*complications/*genetics
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - TCF Transcription Factors/*genetics
MH  - Transcription Factor 7-Like 2 Protein
EDAT- 2008/06/12 09:00
MHDA- 2008/11/15 09:00
CRDT- 2008/06/12 09:00
PHST- 2008/06/12 09:00 [pubmed]
PHST- 2008/11/15 09:00 [medline]
PHST- 2008/06/12 09:00 [entrez]
AID - 10.1055/s-2008-1078720 [doi]
PST - ppublish
SO  - Horm Metab Res. 2008 Oct;40(10):713-7. doi: 10.1055/s-2008-1078720. Epub 2008 Jun 
      10.