TCF7L2 is not a major susceptibility gene for type 2 diabetes in Pima Indians: analysis of 3,501 individuals.
OBJECTIVE
The transcription factor 7-like 2 (TCF7L2) gene was initially reported to be associated with type 2 diabetes in Icelandic, Danish, and U.S. populations. We investigated whether TCF7L2 also has a role in type 2 diabetes susceptibility in Pima Indians.


METHODS
The six variants reported to be associated with type 2 diabetes in the Icelandic study were genotyped in a population-based sample of 3,501 Pima Indians (1,561 subjects had type 2 diabetes, and 1,940 did not have diabetes). In addition, the coding and promoter regions of TCF7L2 were sequenced in 24 Pima subjects. The one variant identified by sequencing, 35 additional database variants positioned in introns, and the six variants reported in the Icelandic study were genotyped in Pima families to determine the haplotype structure of TCF7L2 among Pima Indians. Fourteen representative variants were selected and genotyped in 3,501 Pima Indians.


RESULTS
The six variants initially reported to be associated with type 2 diabetes were less common in Pima Indians compared with samples of European origin, and none were associated with type 2 diabetes. One representative variant, rs1225404, was nominally associated with type 2 diabetes in a general model (additive P = 0.03, dominant P = 0.005) but not in a within-family analysis (additive P = 0.2, dominant P = 0.07). However, several variants were associated with BMI; in particular, rs12255372 was associated in both general and within-family analyses (both P = 0.0007). Modest associations were also found with traits predictive for type 2 diabetes.


CONCLUSIONS
Variation within TCF7L2 does not confer major risk for type 2 diabetes among the Pima Indian population.
Guo
Tingwei
T
Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH, 445 North 5th St., Phoenix, AZ 85004, USA.
Hanson
Robert L
RL
Traurig
Michael
M
Muller
Yunhua Li
YL
Ma
Lijun
L
Mack
Janel
J
Kobes
Sayuko
S
Knowler
William C
WC
Bogardus
Clifton
C
Baier
Leslie J
LJ
D000328:Adult; D001130:Arizona / Q000453:epidemiology; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics; D012016:Reference Values; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein