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Diabetes Publish Ahead of Print published online ahead of print October 1, 2007
DOI: 10.2337/db07-0621
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Original Research

TCF7L2 is Not a Major Susceptibility Gene for Type 2 Diabetes in Pima Indians: An Analysis of 3501 Individuals

Tingwei Guo1, Robert L. Hanson1, Michael Traurig1, Yunhua Li Muller1, Lijun Ma1, Janel Mack1, Sayuko Kobes1, William C. Knowler1, Clifton Bogardus1, and Leslie J. Baier1

1Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, NIDDK, National Institutes of Health, Phoenix, AZ

OBJECTIVE: The transcription factor 7-like 2 gene (TCF7L2) was initially reported to be associated with type 2 diabetes (T2D) in Icelandic, Danish and U.S. populations. We investigated whether TCF7L2 also has a role in T2D susceptibility in the Pima Indians.

RESEARCH DESIGN AND METHODS: The 6 variants reported to be associated with T2D in the Icelandic study were genotyped in a population-based sample of 3501 Pima Indians (1561 subjects had T2D and 1940 were non-diabetic). In addition, the coding and promoter regions of TCF7L2 were sequenced in 24 Pima subjects. The 1 variant identified by sequencing, 35 additional database variants positioned in introns, and the 6 variants reported in the Icelandic study were genotyped in Pima families to determine the haplotype structure of TCF7L2 among Pimas. Fourteen representative variants were selected and genotyped in 3501 Pima Indians.

RESULTS: The 6 variants initially reported to be associated with T2D were less common in Pimas as compared to samples of European origin, and none were associated with T2D. One representative variant, rs1225404, was nominally associated with T2D 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 body mass index (BMI); in particular, rs12255372 was associated in both a general and within family analysis (both P =0.0007). Modest associations were also found with traits predictive for T2D.

CONCLUSIONS: Variation within TCF7L2 does not confer major risk for T2D among the Pima Indian population.

Correspondence: lbaier{at}phx.niddk.nih.gov

Correspondence: lbaier{at}phx.niddk.nih.gov


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