Association testing of TCF7L2 polymorphisms with type 2 diabetes in multi-ethnic youth.
OBJECTIVE
Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been associated with type 2 diabetes in adults. However, it is not known whether TCF7L2 variation increases the risk of early onset type 2 diabetes. Using a case-control design, we examined whether the reported variants [rs12255372 (T/G) and rs7903146 (T/C)] are associated with type 2 diabetes in SEARCH for Diabetes in Youth study participants.


METHODS
Variants were genotyped in 694 non-Hispanic white (NHW) youth (86 cases, mean age 15.5 years, mean BMI 34.8; and 608 controls, mean age 14.4 years, mean BMI 22.3) and 545 African-American (AA) youth (154 cases, mean age 15.9, mean BMI 37; and 391 controls, mean age 14.8, mean BMI 23.8). Logistic regression adjusted for age, sex, BMI and West African ancestry.


RESULTS
The association of the risk T allele with case/control status was different in AA and NHW youth (p = 0.025). Among AA youth, each copy of the T allele (rs7903146) was associated with a 1.97-fold (1.37, 2.82) increased odds for type 2 diabetes (p < 0.0001), after adjustment for age, sex, BMI and African ancestry. No significant association was detected in NHW youth (adjusted OR, 1.14; 0.73, 1.79).


CONCLUSIONS
TCF7L2 variation is associated with an increased risk of early-onset type 2 diabetes among AA youth, and the association appears to be stronger in AA than NHW youth. This suggests potential different contributions of genetic and environmental factors to early-onset type 2 diabetes by race.
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 17th Place, Aurora, CO 80045, USA. dana.dabelea@ucdenver.edu
D
D
Dabelea
L M
LM
Dolan
R
R
D'Agostino
A M
AM
Hernandez
J B
JB
McAteer
R F
RF
Hamman
E J
EJ
Mayer-Davis
S
S
Marcovina
J M
JM
Lawrence
C
C
Pihoker
J C
JC
Florez
D000293:Adolescent; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein